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Inhalt

Oncol Res Treat 2022;45(suppl 1):5

DOI: 10.1159/000521004

Inhalt

Best-of-Abstract-Vortrag

Breast Cancer 18

Cancer Prevention 40

Developmental Therapeutics: Immunotherapy/Cellular 49

Epidemiology 57

Gastrointestinal (Colorectal) Cancer 62

Gastrointestinal (Non-colorectal) Cancer 77

Genitourinary Cancer including Prostate Cancer 95

Gynecologic Cancer 112

Head and Neck Cancer 124

Health Economy/Public Health 133

Leukemia, Myelodysplasia, and Transplantation 140

Lung Cancer 144

Lymphoma and Plasma Cell Disorders 164

Oncological Pharmacy 183

Paediatric Cancer 193

Palliative Care 197

Psychooncology 201

Quality-of-Life 213

Radiation 220

Rehabilitation and long-term burden in social medicine (survivor) 225

Sarcoma 229

Supportive Care 237

Surgical Oncology 252

Poster

Articial intelligence in oncology 7

Biomarker 11

Breast Cancer 18

Cancer of Unknown Primary (CUP) 39

Cancer Prevention 40

Central Nervous System Tumors 44

Developmental Therapeutics: Immunotherapy/Cellular 49

Endocrine Tumors (e. g. thyroid cancer, adrenal tumor, neuroendocrine tumor) 55

Epidemiology 57

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Inhalt

Oncol Res Treat 2022;45(suppl 1):6

DOI: 10.1159/000521004

Gastrointestinal (Colorectal) Cancer 62

Gastrointestinal (Non-colorectal) Cancer 77

Genitourinary Cancer including Prostate Cancer 95

Geriatric Oncology 110

Gynecologic Cancer 112

Head and Neck Cancer 124

Health Economy/Public Health 133

Imaging 138

Leukemia, Myelodysplasia, and Transplantation 140

Lung Cancer 144

Lymphoma and Plasma Cell Disorders 164

MIC/Robotic 174

Molecular Pathology 174

Molecular Therapeutics 176

Novel Agents/Early Clinical Trials 178

Novel developments: Cytotoxic Chemotherapy 179

Nursing in Oncology 180

Oncological Pharmacy 183

Other Topics 184

Paediatric Cancer 193

Palliative Care 197

Psychooncology 201

Quality-of-Life 213

Radiation 220

Rehabilitation and long-term burden in social medicine (survivor) 225

Sarcoma 229

Skin Cancer including Melanoma 235

Supportive Care 237

Surgical Oncology 252

Translational Oncology 254

Autorenindex 264

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Abstracts

Oncol Res Treat 2022;45(suppl 1):7–284

DOI: 10.1159/000521004

Articial intelligence in oncology

Poster

174

Using a RNN-based Dependency Grammar to associate

structured data from histological reports with tissue samples

Julian Dörenberg1; Nadine Gaisa2; Jan Bednarsch3; Lara Heij2,3;

EdgarDahl1,2

1RWTH cBMB Biobank im Institut für Pathologie, Medizinische Fakultät RWTH

Aachen University, Aachen, Deutschland

2Institut für Pathologie, Universitätsklinikum Aachen, Aachen, Deutschland

3Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,

Universitätsklinikum Aachen, Aachen, Deutschland

Background: Availability of structured data is becoming an increasingly

important factor for AI-based analyses of large sets of cancer data. Still,

pathologists in Germany oen record their histological ndings in pathol-

ogy reports using oating text. To aggregate these important tumor-as-

sociated data with further clinical data and cancer samples present in

biobanks, it is critical to convert these report into a structured form. is

can be done by using a Dependency Grammar (DG)1. A recurrent neural

network (RNN) based DG parser is provided by the framework supar2.

Methods: A DG parser trained on non-medical data is used to nd gram-

matical relations between words1. e relations are ltered for requested

data by using UMLS3 and regular expressions.

Result: On 165 sentences randomly selected from breast cancer pathology

reports, the parser correctly generated 97% of the binary relations which

contain medical terms. On a dierent set of 20 reports on hepatocellular

carcinoma the tool successfully extracted 98% of the requested data.

Discussion: e approach passed a proof-of-concept. Although the train-

ing data do not contain medical terms, the parsing accuracy is high on

histological reports. So far, the performance is not aected by the entity

being diagnosed and dierent vocabularies.

Conclusion: DGs can be used to extract data from standard German

pathology reports. As the evaluation corpus so far is very small, it has to be

extended. Aer further evaluation, the tool will eventually provide arbi-

trary information from pathology reports for usage in medical research.

Indication of source:

1. Dozat et. al. Deep Biane Attention for Neural Dependency Parsing. Confer-

ence paper at ICLR, 2017

2. Yan Zhangs. Supar. https://github.com/yzhangcs/parser, 2017

3. Bodenreider. e Unied Medical Language System (UMLS): integrating bio-

medical terminology. In: Nucleic Acids Research, 2004

Disclosure Statement: e authors declare no conict of interest.

594

Automatic extraction of data from medical documents

Georg Emons1; Marcel Markus1; Markus Mandrella1; Maike Greve2;

LutzKolbe2; Michael Ghadimi1; Jens Jakob1

1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin

Göttingen, Deutschland

2Digital Health Research Group (DHRG), Georg-August-Universität Göttingen,

Lehrstuhl für Informationsmanagement, Göttingen, Deutschland

Background: Medical documents are part of daily clinical and research

routine, containing elementary patient data essential for critical tasks

such as estimating prognosis or deciding on individualized tumor therapy.

However, as there is no standardized format for medical documents data

extraction is mostly done by hand. is laborious and numb task is prone

to error, resulting in inconsistent research data or improper treatment

decisions. e aim of this study was to develop and test the reliability of a

digital algorithm extracting the TNM status from pathology-reports.

Methods: Pathology-reports of 600 colorectal cancer patients treated at

the Universitätsmedizin Göttingen (UMG) were obtained in Portable

Document Format (PDF). Using text mining soware we generated an

algorithm to detect, extract and export the Classication of Malignant

Tumors (TNM) status of each patient’s tumor. Results were then com-

pared to manually extracted data from the “Oncostar” database which

is used at the UMG to present data for multidisciplinary tumor boards

and data transfer into the Krebsregister. If conicting data was found, the

original pathology-report was consulted to determine the incorrect data

transfer.

Result: e correctness in the Onkostar-database was as follows T: 92,3%,

N: 98,4%, M: 98,4%, L: 100%, V: 99,5%, R: 99,5%. e correctness of the

automated data extraction algorithm was as follows T: 97,53%, N: 98, 36%,

M: 98,36%, L: 99,59%, V: 100%, R: 98,36%. ere was no statistically dif-

ference between manual and automated data transfer.

Discussion: Despite advances in digital patient data management, up to

this date, there is no standardized, machine readable format for the patho-

logical report used in daily clinical routine. Here we present an algorithm

based on machine learning, automatically extracting TNM-Information

from unstructured reports.

Conclusion: is pilot study demonstrates that automated extraction of

TNM status from pathology reports is feasible and reliable.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts8

689

Identication and classication of tumor cells in Barrett’s

carcinoma patients by Hyperspectral imaging (HSI)

Marianne Maktabi1; Claire Chalopin1; Yannis Wichmann2;

RicardoSchmidt2; Katrin Schierle3; Hannes Köhler1; Ines Gockel2;

RenéThieme2

1Universität Leipzig, Innovation Center Computer Assisted Surgery (ICCAS),

Leipzig, Deutschland

2Univesitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,

Thorax- und Gefäßchirurgie, Leipzig, Deutschland

3Univesitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Deutschland

Background: Discrimination of malignant and non-malignant cells of

histopathologic specimens is a key step in cancer diagnosis. Hyperspectral

imaging (HSI), as recently applied in medicine, as a novel technology

combining imaging with spectroscopy. HSI allows the determination of a

spectrum e.g. between the visual and near-infrared light and it might by

the usage used to identify and classify cancer cells by machine learning

algorithms. Machine learning algorithms are powerful tools for cancer cell

identication and classication using HSI data.

Methods: Aer surgical resection, specimens of Barrett’s carcinoma

(N=96)) and colorectal cancer (N=36) were xed in 4% formaldehyde,

slices were conducted (3µm) and stained with hematoxylin and eosin

(HE). Standard machine learning algorithm for classication were applied.

Result: We were able to analyze esophageal adenocarcinoma (EAC),

tumor stroma and squamous epithelium cells by HSI. Dierences in the

absorbance of squamous epithelium and EAC cells were determined at

eosin’s and hematoxylin’s maximal absorption (530 nm and 590 nm). e

intragroup variances for the squamous epithelium and the esophageal

adenocarcinoma cells were quite low. An accuracy of 71% for EAC and

stroma cells, and 73% for squamous epithelium was achieved by using an

MLP. Furthermore, we distinguish between cancer and healthy tissue in

histopathological slides of colorectal specimens. We achieved a high sen-

sitivity and specicity of 80% and 82%, respectively by using a recurrent

neuronal network combined with a convolutional neuronal network with

a learning rate of 0.001.

Discussion: GI cancer cells show specic spectral alterations due to their

HE-staining, when measured by HSI. However, the training algorithms

need a further validation to foster a semi-automatic decision-making pro-

cess in histopathological tumor cell identication.

Conclusion: However, the histopathological tumor cell identication

needs further validation of the training algorithms to foster a semi-auto-

matic decision-making process.

Disclosure Statement: e authors declare no conict of interest.

870

Prospective, Multi-Center, Articial Intelligence Study for

Early Prediction of Serious Events under Treatment Is Now

Open for Recruitment in Breast Cancer - OMCAT Trial in

Progress

Christian Horst Tonk1,2; Ronald E. Kates2; Sherko Kümmel3;

FatimaCardoso4; Timo Schinköthe2,5; Nadia Harbeck5; Peter Staib6;

AnnetteSchmidt1,7

1Institut für Sportwissenschaft, Universität der Bundeswehr München,

Sportbiologie, Neubiberg, Deutschland

2CANKADO GmbH, Ottobrunn, Deutschland

3Interdisziplinäres Brustkrebszentrum, Kliniken Essen-Mitte, Evang.

Huyssens-Stiftung Essen-Huttrop, Essen, Deutschland

4Breast Unit, Champalimaud Clinical Centre/Champalimaud Foundation, Lisboa,

Portugal

5Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum,

Brustzentrum und CCC München, München, Deutschland

6Sankt Antonius Hospital Eschweiler, Eschweiler, Deutschland

7Forschungszentrum Digitalisierung des Gesundheitswesens, Universität der

Bundeswehr München, Neubiberg, Deutschland

Background: Aim of the OMCAT trial (‘One Million CAncer Treatment

months’, NCT04531995) is improvement of cancer patient care and

safety by developing articial intelligence (AI)-based, incident predic-

tion algorithms. Incident detection allows early notication of treatment

teams, enabling timely management changes or interventions. Ultimately

the algorithms can also support improved health resource allocation.

OMCAT aims to provide learning databases in breast cancer comprising

both electronic patient reported outcome (ePRO) data using the mobile

medical device ‘CANKADO PRO-React’ and ground truth outcome data,

which provide disease-specic events of interest (“incidents”) veried by

the physician (e.g., during patient examinations).

Method: Incident prediction is posed as an application of stochastic time

series analysis using AI and knowledge engineering technology. e learn-

ing process begins by tting individualized and disease-specic stochastic

process models to “incident-free” intervals extracted from the ePRO data

series. Incidents produce detectable deviations from “ordinary” ePRO

uctuations. e algorithms are trained on CANKADO PRO-React data

to produce real-time risk functions for predicting incidents on a clinically

specied time horizon.

Result: Considering heterogeneity and combinatorics of diseases, stages,

therapies, and types of events considered in this study, the AI algorithms

aim to discover about 360 distinct predictive relationships. e estimate

of one million treatment months is derived from statistical power analysis

of this target, considering estimated median documentation time of six

months per patient and estimated 400-500 patients per predictive rela-

tionship. To date, 53 centers in Germany have expressed interest in partic-

ipating. is participation level will enable proof of principle.

Conclusions: OMCAT opens a whole new path towards evidence-trained

AI and a novel combination of patient observation and predictive care.

e goals of OMCAT are ambitious and will therefore require many more

supporters.

Disclosure Statement: e authors declare the following: M.Sc. Christian Tonk

hat ein Anstellungsverhältnis mit der CANKADO GmbH, Dr. Ronald E. Kates hat

ein Angestelltenverhältnis mit der CANKADO GmbH, Prof. Dr. Timo Schinköthe

ist Geschäsführer und Gesellschaer der CANKADO GmbH

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 9

877

Automated QTc Diagnostics for Oncological Routine Via

an AI-based Smartphone APP by Using a Single-Lead ECG

Christian Horst Tonk1,2; Timo Schinköthe2,3; Nadia Harbeck3;

VandaCarmelo4; Joana Gomes Feliciano5; Rachel Würstlein3;

SherkoKümmel6; Annette Schmidt1,7

1Institut für Sportwissenschaft, Universität der Bundeswehr München,

Sportbiologie, Neubiberg, Deutschland

2CANKADO GmbH, Ottobrunn, Deutschland

3Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum,

Brustzentrum und CCC München, München, Deutschland

4Hospital da Luz, Lisboa, Portugal

5Hospital Cruz Vermelha, Lisboa, Portugal

6Interdisziplinäres Brustkrebszentrum, Kliniken Essen-Mitte, Evang. Huyssens-

Stiftung Essen-Huttrop, Essen, Deutschland

7Forschungszentrum Digitalisierung des Gesundheitswesens, Universität der

Bundeswehr München, Neubiberg, Deutschland

Background: Long QT syndrome is a common cardiotoxic side eect of

various anti-tumor drugs. Previous cardiological monitoring of oncolog-

ical patients is primarily complex and requires for non-internal oncol-

ogists a consultation. erefore, the QTc-Tracker smartphone APP was

developed to allow an automatic determination of the QT time using the

smartphone APP. However, since single-lead ECG devices are signi-

cantly more susceptible to interference, the determination of the QT time

is more complex than with 12-lead ECGs.

Methods: Self-tracker single-lead ECG devices were used to record the

lead I signal. e ECG recordings were analyzed in the APP and passed

on to an external cardiologist as reference. e APP used articial intelli-

gence and was trained in the rst phase and validated in the second phase.

e rst phase aimed to improve QT time detection. e results of the

APP were compared with the ndings of the external cardiologist. In both

phases, ECGs from breast cancer patients receiving ribociclib were used.

Result: A total of 1889 single-lead ECGs were carried out. 248 of these

could not be evaluated (13%). QTc prolongation, according to CTCAE,

was diagnosed in 41 cases (2.5%). 878 of the evaluable ECGs were used

for the training phase and 763 for the evaluation phase. In the rst group

(before the improvement), the sensitivity to automatically detect a pro-

longation of the QT time was 36%, and the specicity was 96%. In the

evaluation collective (aer the training), the sensitivity went up to 85%,

and the specicity was unchanged at 96%.

Conclusion: e trained method of the QTc tracker is able to reliably

detect a QT time lengthening even without a cardiological diagnosis only

by using single-lead self-tracker ECG’s. In the rare cases in which an elon-

gation was not detected, the cardiac diagnosis was only a few milliseconds

above the threshold value. is articial intelligence-based smartphone

APP is not intended to replace the cardiological diagnosis, but it can sim-

plify routine processes and help to decide which patients need a cardio-

logical examination more urgently.

Disclosure Statement: e authors declare the following: M.Sc. Christian

Tonk hat ein Anstellungsverhältnis mit der CANKADO GmbH, Prof. Dr. Timo

Schinköthe ist Geschäsführer und Gesellschaer der CANKADO GmbH

899

Using AI to Process Longitudinal Data - a Proof of Concept

Benedikt Sprecher1; Ronald E. Kates2; Christian Horst Tonk2,3;

Timo Schinköthe2,4; Annette Schmidt3,5

1Fakultät für Informatik - Institut für technische Informatik, Universität der

Bundeswehr München, Neubiberg, Deutschland

2CANKADO GmbH, Ottobrunn, Deutschland

3Institut für Sportwissenschaft, Universität der Bundeswehr München,

Sportbiologie, Neubiberg, Deutschland

4Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum,

Brustzentrum und CCC München, München, Deutschland

5Forschungszentrum Digitalisierung des Gesundheitswesens, Universität der

Bundeswehr München, Neubiberg, Deutschland

Background: In various elds outside of medicine, AI-supported systems

have been established that can predict an undesirable event. e purpose

of such systems is to detect events earlier and, if necessary, to be able to

prevent them. In medicine, it would be particularly interesting to be able

to make such predictions based solely on patient observations.

Methods: e usage from 323 patients with advanced breast cancer with

a total of 78542 documentation days was used. In addition, the premature

termination of use was dened as an undesirable event. e data was then

processed and annotated. A deep-learning neural network (NN) classi-

er was trained on this dataset independently on all documented days to

predict this target endpoint. e patient classier score was computed by

averaging over daily scores. Overall classier accuracy and binary cross

entropy loss were computed as performance indicators on training and

test data sets (2:1 split).

Result: Aer tuning the hyperparameters, the best-performing NN

comprised three hidden layers, each with 88 neurons, using ReLU (lin-

ear ramp) activation, and an output layer using sigmoid activation. is

model achieved 98% accuracy on training data with binary cross entropy

loss of 0.5 and 89% accuracy with a similar loss of 0.49 on the test set.

Discussion: An extension of these results will be to model individual

longitudinal data by time series analysis, taking cumulative eects into

account, and to quantify the predictive horizon as an additional key per-

formance indicator for applications.

Conclusion: ese rst results demonstrate that longitudinal medical data,

particularly ePRO data, have predictive value for a clinical target endpoint

and can be modeled using machine learning algorithms. Performance will

generally depend on medical context, available input data, specication of

clinical target endpoints, and statistical and AI modeling details.

Disclosure Statement: e authors declare the following: M.Sc. Christian Tonk

hat ein Anstellungsverhältnis mit der CANKADO GmbH, Dr. Ronald E. Kates hat

ein Anstellungsverhältnis mit der CANKADO GmbH, Prof. Dr. Timo Schinköthe

ist Geschäsführer und Gesellschaer der CANKADO GmbH

980

Validation and Implementation of a Decision Support System

for Quality Assurance of Tumor Boards - Experiences from a

Certied Prostate Cancer Center

Dina Sahi1; David Hoier2; Petra Stamm3; Carolin Groß-Opho-Müller2;

Michael Hallek2; Axel Heidenreich4

1Heilig Geist-Krankenhaus Cologne, Department of Urology, Köln, Deutschland

2University of Cologne, Faculty of Medicine and University Hospital Cologne,

Department I of Internal Medicine, Department I of Internal Medicine, Center for

Integrated Oncology Aachen Bonn Cologne Duesseldorf, Köln, Deutschland

3Heilig Geist-Krankenhaus Cologne, Department of Urology, Köln, Deutschland

4University of Cologne, Faculty of Medicine and University Hospital Cologne,

Department of Urology, Uro-Oncology and robot assisted surgery, Köln,

Deutschland

Background: Certied Cancer Centers must present all patients in mul-

tidisciplinary tumor boards (MTD), including standard cases with well-

established treatment strategies. Too many standard cases can absorb

much of the available time, which can be unfavorable for the discussion

of complex cases. In any case, this leads to a high quantity, but not neces-

sarily a high quality of tumor boards. Our aim was to develop a partially

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts10

algorithm-driven decision support system (DSS) for smart devices to

provide evidence-based recommendations for standard cases of rst-line

therapy of common solid tumors. To assure quality, we compared each

single digital decision with recommendations of experienced MTD and

obtained the concordance rates using the example of prostate cancer.

Methods: 276 prostate cancer patients presented in the MTD of the uro-

logical department of the Heilig Geist-Krankenhaus Cologne from 2018

to 2020 have been evaluated. e questions addressed to MTD were again

answered using DSS. All blinded pairs of answers were assessed for dis-

crepancies by independent reviewers.

Results: Overall concordance rate was 94% (260/276). Stage specic con-

cordance rates were 90% (stage I), 100% (stage II), 87.7% (stage III), and

99.5% (stage IV). Aer independent expert review for cases that were ini-

tially considered non-concordant, the concordance rate could be remark-

ably increased to 100%, 100%, 98.5% and 98.2%.

Discussion: e reliability of any DSS is the key feature before implemen-

tation in clinical routine. Although our DSS seems to be a reliable tool,

continuous adjustment with clinical reality and cross-validation with dif-

ferent hospitals are a necessary requirement to keep up with the dynamic

evolution of therapeutic options.

Conclusion: e quality of therapeutic decisions provided in tumor

boards is perhaps the most relevant criterion for optimal cancer outcome.

is DSS aims to provide optimal recommendations for standard cases,

to relieve tumor boards in favor of complex cases and also to objectively

present the quality of oncology care.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1031

Automated prostate cancer identication facilitates

prognosismarker assessment in11’845 prostate

cancersusing articial intelligence and BLEACH&STAIN

multiplex uorescence immunohistochemistry

Niclas C. Blessin1; Jan H. Müller1; Tim Mandelkow1; Elena Bady1;

Magalie C. J. Lurati1; Claudia Hube-Magg1; Markus Graefen2;

Guido Sauter1; Sarah Minner1; Stefan Steurer1

1Uniklinikum Hamburg-Eppendorf, Pathologie, Hamburg, Deutschland

2Martiniklinik am UKE GmbH, Urologie, Hamburg, Deutschland

Background: Although most prostate cancers behave in an indolent

manner, a small proportion is highly aggressive. To evaluate the patient’s

risk,several prognosis parameters, that can be accompanied by a high

interobserver variability has been established. A reproducible prognostic

evaluation is lacking.

Methods: To enable automated prognosis marker quantication, wehave

developed and validated a framework for automated prostate cancer

detection that comprises three dierent articial intelligence analysis

steps and an algorithm for cell-distance analysis of BLEACH&STAIN

immunohistochemistry. We have used the analysis framework to measure

PSA, PSMA, INSM1, AR, Ki-67, CD56, Chromogranin A, Synaptophysin,

CD8 in a cohort of 11’845 prostate cancers.

Result: e Ki-67 labeling index provided the strongest prognostic

information among all analyzed prognosis marker in 11’845 successfully

analyzed prostate cancers (p<0.001 each). e combined analysis of the

Ki-67-LI and Gleason grades obtained on identical tissue spots showed

that the Ki-67-LI added signicant additional prognostic information

in case of classical ISUP grades (AUC:0.82 [p=0.002]) and quantitative

Gleason grades (AUC:0.83 [p=0.018]). Several combinations of these

8 prognosis markers were combined to prognosis scores and used for

unsupervised clustering to identify a proportion of prostate cancers with

a particularly poor prognosis (p<0.001 each).

Conclusion: Automated prostate cancer identication enables fully auto-

mated prognosis marker assessment in routine clinical practice using

deep learning and BLEACH&STAIN mfIHC.

Disclosure Statement: e authors declare the following: e AR (MSVA-367R),

the INSM1 (MSVA-456R), the Ki-67 (MKI-67/6517R), the Chromogranin A (MS-

VA-380R) and the Synaptophysin antibody clone MSVA-462R were provided from

MS Validated Antibodies GmbH (owned by a family member of GS).

1054

BLEACH&STAIN, a novel multiplex uorescence

immunohistochemistry framework that facilitates a fast

high-throughput analysis of >15 biomarkers in more than

3000 human carcinomas

Elena Bady1; Katharina Möller1; Nicolaus F. Debatin1; Tim Mandelkow1;

Claudia Hube-Magg1

1Universitätsklinikum Hamburg-Eppendorf, Pathologie, Hamburg, Deutschland

Background: Multiplex uorescence immunohistochemistry (mfIHC)

approaches were yet either limited to 6 markers or limited to a small

(1.5cmx1.5cm) tissue size that hampers translational studies on large tis-

sue microarray (TMA) cohorts.

Methods: To assess more markers in a large patient cohort, we have

developed a BLEACH&STAIN mfIHC approach that enables the anal-

ysis of≥15 biomarkers in 3098 tumor samples from 44 dierent carci-

noma entities within one week and without costly instrumentalization.

An articial intelligence-based framework – incorporating three dierent

deep learning systems – for automated marker quantifcation was used to

interoperate the BLEACH&STAIN data.

Result: is approach was used to study the relationship between PD-L1

expression on multiple dierent cell types and the relationship with var-

ious leucocyte subtypes (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163,

CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, CD31). Comparing

the automated and deep learning-based BLEACH&STAIN PD-L1 anal-

ysis framework with conventional brighteld PD-L1 data revealed a

high concordance in tumor cells (p<0.0001) as well as immune cells

(p<0.0001) and an accuracy of our approach ranging from 90% to 95.2%.

Unsupervised clustering showed that a major proportion of the three

PD-L1 phenotypes (i.e., PD-L1+ tumor and immune cells [G1], PD-L1+

immune cells [G2], PD-L1 negative [G3]) were either inamed (G1.1,

G2.1, G3.1) or non-inamed (G1.2, G2.2, G3.2) and showed distinct spa-

tial orchestration patterns.

Conclusion: BLEACH&STAIN mfIHC in combination with a deep learn-

ing-based framework for automated PD-L1 assessment on tumor and

immune cells enabled a rapid and comprehensive assessment of 15 bio-

markers across more than 3000 tumor entities that is quick and easy to

establish in all laboratories. In breast cancer, the PD-L1 relative expression

on tumor cells showed a signicantly higher predictive performance for

overall survival compared to the commonly used PD-L1 tumor propor-

tion score.

Disclosure Statement: e authors declare the following: e PD-L1 (MS-

VA-711R), the CTLA-4 (CTLA4/6864R), the CKpan (PAN-CK/4999R), the

Ki67 (MKI67/6517R), the CD31 (MSVA-031R) and the CD20 antibody clone

IGEL/1497R were provided from MS Validated Antibodies GmbH (owned by a

family member of GS).

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 11

Biomarker

Poster

EarlyCRP kinetics predict long-term treatment success and

favorable outcomes of anti-PD-(L)1 immune checkpoint

blockade in metastatic urothelial carcinoma

Niklas Klümper1,2; Danijel Sikic3; Jonas Saal4; Thomas Büttner1;

JonasJarczyk5; Philip Zeuschner6; Maximilan Weinke7; Charis Kalogirou7;

Johannes Breyer8; Maximilian Burger8; Philipp Nuhn5; Karl Tully9;

FlorianRoghmann9; Christian Bolenz10; Friedemann Zengerling10;

RalphWirtz11; Michael Muders12; Glen Kristiansen12; Jörg Ellinger1;

BerndWullich3; Michael Hölzel2; Arndt Hartmann13; Philipp Erben5;

Manuel Ritter1; MarkusEckstein13

1Universitätsklinikum Bonn, Klinik für Urologie, Bonn, Deutschland

2Universitätsklinikum Bonn, Institut für Experimentelle Onkologie, Bonn,

Deutschland

3Uniklinik Erlangen, Klinik für Urologie, Erlangen, Deutschland

4Universitätsklinikum Bonn, Medizinische Klinik III, Klinik für Hämatologie und

Onkologie, Bonn, Deutschland

5Universitätsklinikum Mannheim, Klinik für Urologie , Mannheim, Deutschland

6Universitätsklinikum des Saarlandes, Klinik für Urologie, Homburg, Deutschland

7Uniklinikum Würzburg, Klinik für Urologie, Würzburg, Deutschland

8Universität Regensburg, Klinik für Urologie, Caritas-Krankenhaus St. Josef,

Regensburg, Deutschland

9Ruhr-Universität Bochum, Klinik für Urologie, Marien Hospital Herne, Bochum,

Deutschland

10Universitätsklinikum Ulm, Klinik für Urologie, Ulm, Deutschland

11Stratifyer Molecular Pathology GmbH, Köln, Deutschland

12Universitätsklinikum Bonn, Institut für Pathologie, Bonn, Deutschland

13Uniklinik Erlangen, Institut für Pathologie, Erlangen, Deutschland

Background: Recently, Fukuda et al. described early on-treatment

C-reactive protein (CRP) kinetics in metastatic renal cell carcinoma that

predicted favorable treatment outcomes [1]. ese early CRP kinetics at

the onset of immunotherapy thus appear to be a promising predictive tool

for monitoring antitumor immune response, and here we aimed to inves-

tigate its potential for predicting ICB response in metastatic urothelial

carcinoma (mUC).

Methods: We conducted a multicenter observational retrospective study

comprising 154 patients with mUC treated with ICB to evaluate the pre-

dictive value of on treatment CRP kinetics. ree CRP kinetics groups

were dened: CRP are-responders (initial doubling of baseline CRP and

subsequent decrease below baseline), CRP responders (decrease of at least

30% of baseline CRP) and CRP non-responders. CRP kinetics groups

were correlated with baseline parameters, PD-L1 status (combined posi-

tivity score, CPS), progression-free (PFS) and overall survival (OS).

Result: Objective response according to RECIST v1.1 were observed in

57.1% of CRP responders, 45.8% of CRP are-responders and 17.9% of

CRP non-responders (P<0.001). CRP are-response was associated with

prolonged PFS and OS (P<0.001) while PD-L1 measured by CPS failed to

predict responses or outcomes. In multivariable Cox regression analysis,

CRP are-responders showed a risk reduction of ~70% for tumor progres-

sion an death compared to CRP non-responders.

Discussion: Future prospective studies with standardized CRP sampling

schedules are required to validate the predictive and prognostic CRP

are-response predicts ICB success value of CRP kinetics.

Conclusion: CRP (are-)responses robustly predict immunotherapy

response and outcomes in mUC independent of PD-L1 status. us, early

on-treatment CRP kinetics is a promising low cost and easy-to-implement

biomarker to optimize therapy monitoring in patients with mUC treated

with ICB.

Indication of source:

[1] PMID: 33602695

Disclosure Statement: e authors declare no conict of interest.

117

Claudin 18 Isoform Expression in Gastric Adenocarcinoma

andPancreatic Adenocarcinoma

Takeshi Saito1; Takashi Matsuda1; Diarmuid Moran1; Stefan Langhammer2

1Astellas Pharma, Inc., Northbrook, USA

2Astellas Pharma GmbH, München, Deutschland

Background: e claudin 18 (CLDN18) protein has two isoforms:

CLDN18.1 and CLDN18.2. CLDN18.2 is the dominant isoform expressed

in gastric adenocarcinoma (GA) and pancreatic adenocarcinoma (PA);

thus, it has emerged as a targetable biomarker. Zolbetuximab, a chimeric

IgG1 monoclonal antibody, binds specically to CLDN18.2 and mediates

cancer cell death via antibody-dependent cellular cytotoxicity and com-

plement-dependent cytotoxicity. Zolbetuximab study results highlight the

importance of selecting patients with CLDN18.2–positive cancer; how-

ever, CLDN18 isoforms are dicult to dierentiate at the protein level.

is study aimed to explore and conrm expression patterns of CLDN18

isoforms in a large dataset.

Methods: Relative CLDN18.1 and CLDN18.2 expression was analyzed

using bioinformatics mining of the TCGA database. TCGA RNA-Seq data

for GA (n=416) and PA (n=178) were analyzed for isoform expression

values by counting reads mapped on specic exons of both isoforms. Data

were expressed as fragments per kilobase of exon model per million reads

mapped (FPKM).

Result: Median expression values of CLDN18.2 and CLDN18.1 were 48.6

and 0.453 FPKM, respectively, in GA and 19.9 and 0.352 FPKM, respec-

tively, in PA. CLDN18.1 expression was below baseline (<0.5 FPKM) or

low (0.5-10 FPKM) in 95% of GA samples and in 100% of PA samples. In

contrast, CLDN18.2 was detectable above 10 FPKM in 69% of GA samples

and in 61% of PA samples with 38% and 16% of samples, respectively,

expressing CLDN18.2 ≥100 FPKM. A comparison of median isoform

expression in samples with CLDN18.1 expression detected above baseline

(>0.5 FPKM) demonstrated a 93-fold and 92-fold higher median expres-

sion of CLDN18.2 over CLDN18.1 in GA and PA, respectively.

Discussion: Results conrm that CLDN18.2 is the more dominantly

expressed isoform in a large dataset of GA and PA cases. Negligible

CLDN18.1 RNA expression suggests that meaningful protein expression

would not be anticipated.

Conclusion: ese results indicate that detection of total CLDN18 protein

is representative of CLDN18.2 expression in PA and GA.

Disclosure Statement: e authors declare the following: All authors are

employees of Astellas Pharma, Inc.

325

Biomarker panel predicts response to MEK inhibition in

colorectal cancer

Ulrike Pfohl1,2; Jürgen Loskutov1; Sanam Bashir3; Ralf Kühn4;

MarkusTemplin5,6; Gerrit Erdmann6,7; Soulafa Mamlouk8; Sergei Belanov9;

Christoph Reinhard1,6; Lena Wedeken1; Christian Regenbrecht1,6,10

1CELLphenomics GmbH, Berlin, Deutschland

2Goethe-Universität Frankfurt am Main, Frankfurt am Main, Deutschland

3BioNTech SE, Mainz, Deutschland

4MDC Berlin (Max-Delbrück-Centrum für Molekulare Medizin), Berlin,

Deutschland

5NMI Naturwissenschaftliches und Medizinisches Institut, Reutlingen,

Deutschland

6ASC Oncology GmbH, Berlin, Deutschland

7NMI TT GmbH, Berlin, Deutschland

8Charité – Universitätsmedizin Berlin, Institut für Pathologie, Berlin, Deutschland

9Universität Helsinki, Helsinki, Finnland

10Universitätsmedizin Göttingen, Institut für Pathologie, Göttingen, Deutschland

Background: In colorectal cancer (CRC) mutations in the TGF-β/

BMP pathway, particularly in the SMAD4 gene have been correlated

with decreased overall survival and are suspected to be responsible for

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts12

chemoresistance (1, 2). erefore, there is a critical need for recogniz-

ing therapeutic agents, capable of targeting SMAD4 mutated tumors. In

the present study, we uncover the mechanistic role of SMAD4R361H using

oncoproteomics in syngeneic CRISPR-engineered SMAD4R361H CRC

patient-derived organoids (PDO).

Methods: We investigated multiple PDO from a single CRC tumor that

dier only by SMAD4R361H mutation. Using CRISPR-Cas9 approach, we

introduced R361H into SMAD4 wildtype PDO. Organoid cultures were

subjected to a comparative drug screening, RNA-Sequencing and subse-

quent multiplex protein proling analysis (DigiWest®).

Result: SMAD4R361H PDO were more sensitive to MEK inhibition com-

pared to their SMAD4 wildtype counterparts. Out of SMAD family

proteins, only SMAD5 showed changes in protein level and phosphor-

ylation status in response to MEK-inhibition, both were increased only

in SMAD4wt PDO. We tested over 50 CRC models and discovered up to

95% and 79% signicant positive prediction for the MEK inhibitors cobi-

metinib and trametinib, respectively, for models with disruption in the

TGF-β/BMP pathway.

Discussion: BMP signaling promotes cancer cell proliferation and tumor

growth (3). It is plausible to assume, that functional loss of SMAD4 and

thus loss of SMAD5 signaling render SMAD4R361H subpopulation of

cells more sensitive to MEK inhibitors. We propose to use the status of

SMAD4, ARID1A, BMPR2, and FBXW7 as a biomarker for considering

MEK inhibitors to achieve a clinical benet for cancer patients.

Conclusion: A disruption in the BMP pathway through loss-of- function

mutation or deletion in SMAD4, ARID1A, BMPR2, and FBXW7 is

responsible for the sensitivity towards MEK-inhibition in CRC.

References:

1. A. M. Sarshekeh et al., Plos One. 12, e0173345–e0173345 (2017).

2. M. Zhao, L. Mishra, C. X. Deng, Int J Biol Sci. 14, 111–123 (2018).

3. J. Peng et al., Mol Carcinogen. 55, 335–45 (2015).

Disclosure Statement: e authors declare no conict of interest.

385

The App “Präzisionsonkowissen - Pow”: State of the Art

Precision Oncology – combining scientic and clinical

knowledge

Tanja Grimmig1; Carine Nguemeni1; Sarah Schuster1; Friedrich Schütze1;

Christina Jessen1; Viktoria von Krosigk1; Thomas Spall2; Erik Belleville2;

Friedrich Overkamp2

1ClinSol GmbH & Co. KG, Würzburg, Deutschland

2onkowissen.de GmbH, Würzburg, Deutschland

Precision oncology is evolving at a fast pace and has entered the main-

stream of clinical practice. It is dened as the molecular proling of

tumors to identify targetable alterations. is allows for a personalized

treatment based on matching biomarkers and individual characteristics of

the patient’s cancer to targeted molecular therapies. With the treatment of

cancer moving from traditional approaches towards precision medicine,

the need for in-depth scientic knowledge about this eld is continuously

growing as well as up-to-date information regarding available therapeutic

options.

e universal app “Präzisionsonkowissen” (aka Pow) supports this

transition by oering a broad spectrum of useful information/tools for

everyday clinical practice. Pow contains relevant back-ground informa-

tion about the individual biomarkers, their function and biological signif-

icance in oncology.

A specic chapter covers innovative approaches to comprehensive

molecular, cellular and functional analysis of the alteration status of

tumors. Analytical methods and concepts are particularly highlighted,

including multimedia insights into clinical pathology. e app also pres-

ents the latest approved biomarker-targeted standard therapies, in con-

formity with evidence-based guidelines and approval studies. Further, a

particular focus is on new options for targeted treatments including o/

no-label therapies and therapies in an advanced stage of development. A

special feature is the newsfeed, which informs the user about novelties in

the eld, such as relevant studies or new EMA/FDA approvals. Finally,

Pow oers the possibility to dene favorites and to create a personalized

quick access to the most relevant content of the respective chapters.

Pow is an innovative, interactive and educational app database collec-

tion of high-grade information on precision oncology. It supports clinical

daily routine including the preparation for molecular tumor boards and

the feature of keeping up-to-date in best-practice therapies, as well as in

o-label/no-label treatments.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

446

Detection of cfHPV16-DNA in liquid biopsy - A promising

biomarker for patients with HPV-related oropharyngeal

squamous cell carcinoma

Nora Würdemann1; Christina Alidousty2; Oliver Siefer1; Rishabh Jain1;

Christian Ulrich Hübbers1; Ste Silling3; Darius Schagh4; Robin Bacher5;

Henrike Reder6; Reinhard Büttner2; Markus Dietlein5; Alexander Drzezga5;

Marc Schlamann4; Ulrike Wieland3; Alexander Quaas2; Claus Wittekindt7;

Ernst-Jan Speel8; Steen Wagner6; Anne Schultheis2; Jens Peter Klußmann1

1Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Uniklinik Köln, Köln,

Deutschland

2Institut für Pathologie, Uniklinik Köln, Köln, Deutschland

3Institut für Virologie, Uniklinik Köln, Köln, Deutschland

4Institut für Diagnostische und Interventionelle Radiologie, Uniklinik Köln, Köln,

Deutschland

5Klinik und Poliklinik für Nuklearmedizin, Uniklinik Köln, Köln, Deutschland

6Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Uniklinik Gießen,

Gießen, Deutschland

7Klinik für Hals-Nasen-Ohrenheilkunde, Klinikum Dortmund, Dortmund,

Deutschland

8Institut für Pathologie, Uniklinik Maastricht, LK Maastricht, Netherlands Antilles

Background: Incidences of oropharyngeal squamous cell carcinoma

(OPSCC) associated with high-risk Human Papillomavirus (HPV) are

steadily increasing worldwide. Although HPV-related OPSCC are accom-

panied by a signicantly better 5-year overall survival compared with

HPV-negative OPSCC, 25% still develop locoregional recurrence or dis-

tant metastases. Biomarkers to monitor therapy response and disease pro-

gression are lacking to this point.

Methods: In a multicenter study, the concentration of cell-free (cf)

HPV16-E6/E7 DNA in plasma was measured by quantitative (q)PCR /

droplet digital (dd)PCR at initial diagnosis and during follow-up in

patients with OPSCC (test-cohort n = 37; validation-cohort n = 53). e

copy number (cn) of cfHPV16-E6/E7 DNA in plasma was subsequently

correlated with the course of disease as well as imaging and clinicopatho-

logical parameters.

Result: In the test-cohort, ROC-Analysis revealed an outstanding dis-

crimination in ddPCR (AUC = 0.9256) and qPCR (AUC = 0.9467).

Furthermore, elevated cfHPV16-DNA E7 cn detected by ddPCR cor-

related with higher T-stage (p ≤ 0.050). In our validation-cohort, ROC-

Analysis revealed discrimination only in E6-ddPCR and no correlation

of median cfHPV16-DNA cn with T- or N-stage was detected in either

PCR method. Nevertheless, cfHPV16-DNA cn correlated with metabolic

tumor volume in 18F-FDG-PET-CT (r = 0,5982; R2 = 0,3578; p = 0,0012).

A signicant reduction of cfHPV16 E6 DNA levels was detected in both

cohorts post-therapeutically (p ≤ 0.001), whereas an increase in copy

number correlated with recurrence or distant metastasis.

Discussion: ddPCR demonstrated to be more sensitive than qPCR for

the detection of cfHPV16-DNA in plasma of patients with HPV-related

OPSCC and tumor stage and metabolic tumor volume inuence the

amount of cfHPV16-DNA shed into the blood stream.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 13

Conclusion: cfHPV16-DNA in plasma of patients with HPV-associated

OPSCC represents a promising biomarker for monitoring the course of

disease. Prospective studies with larger cohorts are needed to validate

these results.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

568

Decreased expressions of CD44v4 and CD44v10 correlate with

earlier tumor progression

Michael Modrok1; Undine Tiller1; Rosa Rühl1; Peter Baumgarten1;

ChristianSenft1; Arend Koch2; Jan Walter1,3; Diana Freitag1

1Department of Neurosurgery, University Hospital Jena, Jena, Deutschland

2Department of Neuropathology, Charitè - Universitätsmedizin Berlin, corporate

member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin,

Deutschland

3Department of Neurosurgery, Medical Center Saarbruecken, Saarbrücken,

Deutschland

Background: e transmembrane glycoprotein CD44 is widely used to

identify tumor stem cells (CSCs). However, CD44 controls a variety of

processes, making the identication of CSCs very dicult. Due to alter-

native splicing, there are 10 variable forms of CD44 (CD44v1-v10) besides

the stable form CD44s, each with dierent properties in tumor biology.

e aim of this study was to evaluate the expression of dierent CD44

isoforms in human meningiomas and to assign specic cell properties to

their expressions by correlation with clinical data.

Methods: RNA was isolated from 80 specimens of individual meningioma

patients and analyzed by quantitative polymerase chain reaction (qPCR).

Expression of CD44s as well as CD44v1-v10 was analyzed. e correla-

tions of the expression data with the clinical data was analyzed in terms of

progression-free survival (PFS) at a monitoring interval of 2 years (n=68)

aer prior ROC analysis (Kaplan-Meier).

Result: Gene expressions from CD44v3 to CD44v10 were found in the

majority of samples. Only for CD44s and CD44v3, higher relative expres-

sion values could be detected in meningiomas as compared to control

tissue (dura mater). However, subgroup analyses revealed that the mean

relative expressions for CD44 variants v4, v5, v7, v8 and v9 and v10

showed signicant dierences between WHO grade I or II and control

tissue. Subsequent Kaplan-Meier analysis for PFS indicated that high

expression levels of the v4 and v10 isoforms were associated with better

outcome, particularly in male patients.

Discussion: ese analyses provide rst hints at a possible involvement of

the individual CD44 isoforms in the progression of human meningiomas.

In addition, there is evidence that the v4 and v10 isoforms play a protec-

tive role in tumor progression.

Conclusion: CD44 isoform expression may potentially aect tumor pro-

gression in meningiomas, rendering them a potential target for therapeu-

tic approaches in meningioma treatment.

Disclosure Statement: e authors declare no conict of interest.

586

Serum proteins as predictive markers of the response to

neoadjuvant chemotherapy for breast cancer

Ines Derya Steenbuck1; Miguel Cosenza2; Klemens Fröhlich2;

Bettina Mayer3; Tilman Werner2; Markus Jäger1; Daniela Weiß1;

Claudia Noething1; Oliver Schilling2; Thalia Erbes1

1Department of Obstetrics and Gynecology, Medical Center - University of

Freiburg, Freiburg, Deutschland

2Institute of Surgical Pathology, Medical Center - University of Freiburg, Freiburg

3Institute of Molecular Medicine and Cell Research , University of Freiburg,

Freiburg, Deutschland

Breast cancer continues to be the most common cancer type among

women in Germany and worldwide. Over the last years neoadjuvant

chemotherapy NACT represents an increasingly important role as a

standard therapy-regimen . Because of the correlation of pathological

complete response (pCR) and long-term clinical prognosis there is a need

to monitor therapy-response in term of therapy adaption. Until now,

breast-ultrasound represents the method of choice for progress-evalua-

tion during NACT. In this proof-of-concept, retrospective longitudinal

cohort study, we had the purpose to nd an additional method for ther-

apy-response validation by liquid biopsy. Serum samples from patients

suering from breast cancer of the subtype Luminal B (Her2/neu -) and

TNBC were examined during NACT with 4x epirubicin and cyclophos-

phamide (EC)+ 12x paclitaxel. 11 complete responders (CR) with pCR

and 11 non-responders (NR) with non-pCR, >ypT0, were included. In

addition to, 24 sera from healthy women were also included as a control

group. Samples were taken before the rst cycle of EC (t0), before the third

cycle of EC (t1) and before the third cycle of Paclitaxel (t3). As method of

choice, we used immunoanity depletion of 14 high abundant proteins,

followed by Lys-C + Trypsin Co-digestion, clean up, isobaric labelling,

fractionation by high-pH reversed-phase liquid chromatography, and

LC-MS/MS-measurement. We were able to demonstrate a signicant

reaction to the NACT in the proteomic prole at timepoint t1 and t3 com-

pared to timepoint t0. Furthermore, 5 potential marker candidates were

identied, which show a dierent intensity behaviour between the groups

NR and CR (HGF receptor, N-cadherin, Centrosomal protein 192 kDa,

Contactin 1, Cholinesterase). N-cadherin should be emphasized, due

to an inverse behaviour with an increase of intensity at t1 in CR and a

decrease of intensity at t1 in NR. e present ndings lay the foundation

to expand the study with a larger patient number.

Disclosure Statement: e authors declare no conict of interest.

661

Kidney cancer urine marker

Barbara Köditz; Jochen Fries; Jan Herden; Manuel Huerta;

AxelHeidenreich; Melanie von Brandenstein

Uniklinik Köln , Urologie, Köln, Deutschland

Background: : Recently, our group showed that Vim3 is overexpressed in

tissue samples of renal oncocytomas and Mxi-2 in clear cell renal carci-

noma (ccRCCs). e mechanism leading to the truncation of both pro-

teins is known and involves with two miRs, both detectable in urine. Since

the analysis of miRs is time consuming, our aim was to identify the trun-

cated proteins in urine instead. Furthermore, urine samples from small

renal cancers (SRM) (n=45, <4 cm) were analyzed to get a pre-surgical

dierentiation of the cancer subtypes.

Methods: Urines were accessed from the urological biobank (n=350).

Proteins were isolated from urine samples, and Western blots were per-

formed. Each sample was analyzed with ELISA for the expression of Vim3

and Mxi-2. A lateral ow assay was established. For the detection of SRMs,

the miRs were isolated and qRT-PCR was performed.

Result: A signicant increase of Vim3 in urines from patients with onco-

cytoma (n=20) was detectable with ELISA compared to all other subtypes

of RCCs (chromophobe (n=50), papillary (n=40), ccRCC (n=200), and

controls (n=40) (***p<0.0001)). Mxi-2 was predominantly overexpressed

in ccRCCs (***p<0.0001). Lateral ow assay of Vim3 and Mxi-2 shows

two bands in the case of oncocytoma and ccRCC indicating the specicity

of this test. For SRMs, an overexpression of miR-15a/Mxi2 was detectable

in urine samples from ccRCC and chromoRCC patients. In contrast to

that miR-498/Vim3 were predominantly overexpressed in oncocytoma

patients.

Discussion: Here two dierent expression patterns were identied based

on the type of kidney tumour. Also the size of the kindey tumor do not

play a role in the signicant of the data.

Conclusion: Both proteins (Vim3 and Mxi-2) were detectable in patients’

urines and can be used for the non-invasive dierentiation of kidney

cancers.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts14

669

Assessment of genetic tumor proles and clonal evolution

byliquid biopsy: The Augsburger Longitundinal Plasma

Study(ALPS)

Sebastian Sommer1; Maximilian Schmutz1; Sebastian Dintner2;

Maria Campillo1; Maria Eberle1; Yvonne Silber1; Angela Langer2;

Bruno Märkl2; Matthias Schlesner3; Simone Hummler1; Boris Kubuschok1;

Martin Trepel1; Rainer Claus1

1Universitätsklinikum Augsburg 2. Medizinische Klinik, Augsburg, Deutschland

2Universitätsklinikum Augsburg, Institut für Pathologie und molekulare

Diagnostik, Augsburg, Deutschland

3Institut für Informatik , Biomedizinische Informatik, Data Mining und Data

Analytics, Augsburg, Deutschland

Background: Analyzing circulating tumor DNA (ctDNA) from liquid

biopsy (LBx) allows diagnostic and prognostic assessment and disease

course monitoring of malignancies. However, the clinical application

of ctDNA assessment is still limited. ALPS is a trial and a LBx-banking

resource that aims at bridging the gap of LBx from translational research

to routine clinical practice by investigating key questions: (a) the concor-

dance of LBx and tissue biopsy (TBx); (b) the relevance of LBx for fol-

low-up and disease progression; (c) the applicability of LBx to display

clonal heterogeneity and evolution upon treatment and progression.

Methods: ALPS is a prospective observational study of an anticipated

number of n=1000 patients (pts) over 4 years with metastatic cancers. At

time of enrollment, tumor TBx and initial LBx from peripheral blood (PB)

are obtained. Serial PB samples are collected every 3 months concurrently

with standard staging evaluations. Circulating cell free DNA (ccfDNA) is

analyzed using CAPP-seq. Genomic characterization of tumor TBx and

controls is performed by WES.

Result: Recruitment started in April 2021, 86 patients have been enrolled

in the pilot phase. Median age is 63 years (range 29-89), 27% are women.

Pts with NSCLCs were most common (n=17), followed by SCLC (n=8),

pancreatic (n=7) and colon cancer (n=5), CUP (n=5), esophageal cancer

(n=5), and other entities. ccfDNA was isolated from 91 plasma samples of

78 pts. ccfDNA amounts ranged from 0,24 ng to 12,96 µg. Sequencing of

ccfDNA from the rst 8 pts yielded46 to 68M reads with an on-target rate

of 40-80% and a detection sensitivity of 0.1%. Cancer-related mutations

and CNVs were identied in all 8 samples.

Conclusion: Here we describe a study and infrastructural resource

(ALPS) for the systematic evaluation of LBx in metastatic tumors. In the

the pilot phase, we demonstrate that ccfDNA can be obtained in sucient

quantity and quality for successful genomic analyses in patients with dif-

ferent metastatic malignancies. e design of ALPS is suitable to address

questions relevant to routine clinical application of LBx.

Disclosure Statement: e authors declare no conict of interest.

680

In-depth methylation analysis of the epigenetic marker

regions ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671

incervical precancerous lesions and cervical carcinoma

Lars Jansen1; Katrin Beer1; Martina Schmitz2; Alfred Hansel2;

Ingo B. Runnebaum1; Matthias Dürst1

1Gynäkologische Molekularbiologie, Universitätsklinikum Jena, Klinik und

Poliklinik für Frauenheilkunde und Fortpanzungsmedizin, Jena, Deutschland

2oncgnostics GmbH, Jena, Deutschland

Background: Cervical carcinoma is the fourth most common cancer in

women worldwide. In carcinogenesis, local DNA hypermethylation oen

occurs in cytosine- and guanine-rich DNA regions called CpG islands,

which are frequently located in promoter regions. e aim of this work

was to investigate the extent to which methylation of CpG islands associ-

ated with the genes ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671,

can be attributed to tumor or dysplastic cells and thus represent a direct

phenomenon of cervical carcinogenesis.

Methods: From deep-frozen tissue sections, 30 carcinomas and 18 CINs,

tumor and dysplastic cells, respectively, as well as adjacent stroma cells

were manually microdissected. Chemical bisulte treatment was used to

convert the methylation information into a sequence dierence. rough

bisulte-specic PCR the DNA regions of interest were amplied, and

methylation within these regions was determined via next-generation

sequencing.

Result: Depending on marker regions, methylation in tumor cells was 6-

to 57-fold higher than in stromal cells. In tumor areas methylation was

> 70% for the marker regions ASTN1, DLX1, SOX17, and ZNF671 and

> 47% for ITGA4 and RXFP3 in the sample set tested. In contrast, stro-

mal cell methylation is ≤ 4.1% for ASTN1, ITGA4, RXFP3, SOX17 and

ZNF671 markers. DLX1 showed a signicantly higher baseline methyla-

tion of 14.2%. In addition, DNA methylation was shown to increase with

the severity of cervical lesions, from average of 5.6% in CIN1, to 8.6% in

CIN2, to 22.5% in CIN3.

Discussion: Methylation changes in the six marker regions ASTN1, DLX1,

ITGA4, RXFP3, SOX17 and ZNF671, the detection of which provides the

basis for the molecular cancer diagnostic GynTect, indeed occurs in the

dysplastic and the tumor cells, not in the surrounding tissue.

Conclusion: Methylation of the six marker regions is at least a conse-

quence of, if not even the cause for cervical carcinogenesis.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

698

Vim3 – a new surrogate marker for prostate cancer

Melanie von Brandenstein; Barbara Koeditz; Jochen Fries;

Axel Heidenreich

University Hospital of Cologne, Clinic and Polyclinic for Urology, Cologne,

Deutschland

Background: Prostate cancer (PCa) is the most frequently diagnosed

malignancy in elderly men. e determination of Vim3 in patients’ serum

can be an important new biomarker for the determination of the biologi-

cal aggressiveness of PCa. In our opinion, the measurement of Vim3 levels

in the serum might predict the aggressiveness and prognosis of PCas.

Methods: We reviewed serum samples from 350 male patients during the

years 2015 to 2018 from our department. Control group: patients without

cancer background, median PSA < 4.0 ng/ml. Low risk group: Gleason 6,

median PSA 7.4 ng/ml. Intermediate risk group: Gleason 7a-7b, median

PSA 14.9 ng/ml. High risk group: Gleason >8, median PSA 30.4 ng/ml

without visible metastases on routine imaging studies such as Bone scan

and CT scans of the abdomen and the small pelvis. Metastasis group:

patients with osseous or visceral metastasis at time of rst diagnosis,

median PSA 64.4 ng/ml. Recurrence group: patients with recurrence (PSA

relapse and metastasis), median PSA 41.3 ng/ml. Vim3 ELISA was estab-

lished previously and performed with 50 µl patient serum.

Result: Via ELISA it could be demonstrated that the Vim3 protein level

increased signicantly (p<0.001) with increasing biological aggressiveness

of human PCa specimens from prostate biopsies and/or radical prostatec-

tomy specimens (Gleason ≥8, independent of the pT stage). Furthermore a

clear cut-o value for Vim3 level was determined(cut-o 300-350ng/ml).

Discussion: Vim3 could be a new biomarker for PCa, especially for PCa

with increasing metastatic potential. In our opinion, Vim3 values above

a predetermined cut of level could support the suspicion of a high grade

PCa even if PSA and Gleason grade aer biopsy do not (yet) indicate the

presence of a high grade PCa.

Conclusion: Serum Vim3 levels rise with increasing malignancy of the

prostate cancer and correlate with the Gleason Score and therefore could

be usable as novel surrogate marker for prostate cancer

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 15

701

EBV induced regulation mechanism in metastasized

and non-metastasized seminoma

Barbara Köditz1; Yasmine Maatoug1; Tim Nestler1; Jochen Fries1;

PiaPaenholz1; David Nicol2; Axel Heidenreich1;

Melanie von Brandenstein1

1Uniklinik Köln , Urologie, Köln, Deutschland

2The Royal Marsden NHS Foundation Trust, Consultant Urological Surgeon,

London, Vereinigtes Königreich

Background: Epstein-Barr Virus (EBV) has the ability to induce a regula-

tion mechanism that results in the down regulation of the truncated ver-

sion of Vimentin 3 (Vim3), a metastasizing marker. e presence of EBV

is responsible for the upregulation of miRNA 199-3p, which downregu-

lates Endothelin-1 (ET-1) by binding its 3’ UTR. ET-1 induces the produc-

tion of Vim3. Since the described regulation mechanism was identied in

clinical stage I seminomas with uneventful follow-up we hypothesized an

opposite mechanism will occur in metastasized seminomas.

Methods: For the investigation of the regulation mechanism tissue biop-

sies from primary orchiectomy specimens with pure, classic seminoma

of clinical stage IIC/III patients and from resected retroperitoneal lymph

node metastases of clinical stage IIA/B seminoma patients were analysed.

Total RNA was isolated from macrodissected paran embedded tissue

areas. e expression of the miRNA 199-3p, EBNA-1, ET-1 and Vim3 was

determined via qRT-PCR. Furthermore, the expression of EBER-1 and

Vim3 was analyzed via immunohistochemistry.

Result: Via immunohistochemistry and qRT-PCR no EBER expression

was present in primary tumors and lymph node metastases. Furthermore,

down regulation of the miRNA 199-3p and an up regulation of ET-1 and

Vim3 were detectable.

Discussion: In case of metastasized seminoma no EBV infection was

detectable neither in the tumor sample nor in metastases which resulted

in an increased expression of ET-1 and Vim3 and downregulation of

miR-199 contributing to the metastatic process of pure seminomas.

Prospective validation of these ndings is under way to proof that those

molecular events might be used as a biomarker for high risk disease

triggering adjuvant therapy following radical orchiectomy. Whether the

upregulation of the miR-199 can be used as metastasizing inhibitor needs

to be evaluated further.

Conclusion: To summarize a regulation mechanism induced by EBV

wasidentied.

Disclosure Statement: e authors declare no conict of interest.

708

A new signal transduction pathway for AR in urothelial

carcinoma

Melanie von Brandenstein1; Julie Brunner1; Barbara Koeditz1; Manuel

Huerta1; Maximillian Schmautz1; Axel Heidenreich1

1University Hospital of Cologne, Clinic and Polyclinic for Urology, Cologne,

Deutschland

Background: Since, it is already known that bladder cancers with elevated

endothelin-1 (ET-1) levels have a higher metastasizing potential. For the

early detection of urothelial carcinoma, the analysis of elevated levels of

molecules in the patients’ blood or urine is of great interest. Our group

could recently show that patients with a muscle invasive bladder cancer

(MIBC) have higher levels of ERß in the blood.

Methods: e urinary bladder cancer cell line HTB-9 were cultivated as

recommended and treated with ET-1 and ET-1 receptor blockers (BQ123

and BQ788). Pull down assays with the androgen receptor (AR) and the

miR-708 were performed. Western Blot aer dierent treatment options

and qRT-PCR were established. Furthermore, we analysed via ELISA

urine samples from patients with bladder cancer (n=35) and control

healthy donors (n=15).

Result: In HTB-9 cells, we identied a novel mechanism, which is respon-

sible for the E-cadherin downregulation in urothelial carcinoma. ET-1

forms a complex with the AR in the cytoplasm and migrates into the

nucleus. e newly identied complex is important for the transcription

of the estrogen receptor beta (ERß). We were able to show that the ERß

overexpression leads to an increased expression of miR-708. It is known,

that this miR can bind to the 3’UTR of E-cadherin and acting as onco-miR.

Discussion: We identied an ET-1 dependent mechanism leading to the

overexpression of specic biomarkers and the downregulation of tumor-

genes in urinary bladder cancers. In urine samples, a signicant overex-

pression of ET-1 and ERß and a resulting downregulation of E-cadherin

was detectable in bladder cancer patients.

Conclusion: e analysis of such biomarkers could be probably used in

future for the evaluation of urothelial carcinoma.

Disclosure Statement: e authors declare no conict of interest.

777

Clinically relevant prognostic biomarkers for immune

checkpoint inhibitor therapy in NSCLC

Gloria Zeitler1; Wolfgang Brückl1; Joachim Ficker1

1Klinikum Nürnberg Nord, Nürnberg, Deutschland

Background: We investigated the association of clinical and laboratory

ndings with response and treatment eects in immune-checkpoint

inhibitor (ICI) therapy treated advanced NSCLC patients.

Methods: NSCLC patients receiving at least one dose of ICI therapy at the

Lung Cancer Center Nuremberg between 2016 and 2019 were identied

retrospectively. Factors associated with PFS or OS were assessed with Cox

proportional hazard models. A prognostic score (∆-Score) combining

∆LDH, ∆CRP and ∆G-GT created and categorizes patients into prognos-

tic subsets.

Result: Among 89 patients, 66.3% were men, median age was 68 years

and 70.8% received pembrolizumab as 1st line treatment. For the whole

cohort, median PFS and OS was 5 months and 11.2 months, respectively.

Median PFS was 5.7 months and median OS was 12.7 months in the 1st

line therapy cohort. On multivariate analysis, an increasing ∆LDH (p =

0.043), NLR < 5 (p = 0.045) and CRP-Q1 (≤ 7.7 mg/dL) (p = 0.033) were

signicantly associated with superior median PFS. CRP-Q1 was also asso-

ciated with a greatly enhanced median OS for the whole cohort. A low

∆-Score reached a high level of signicance in terms of PFS and showed a

clear trend regarding OS.

Discussion: ere are several limitations to this study, e.g. the cut-o val-

ues of the laboratory ndings were not adapted to patients‘ gender and

chosen by using the standards determined by the local laboratory without

investigating their devisive character.

Conclusion: Our results demonstrate that laboratory measurements

are eective tools in the prediction of response and outcome in NSCLC

patients treated by ICI. Further studies are warranted to conrm their

prognostic signicance in this patient population.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts16

990

Antitumor activity of dostarlimab by PD-L1 and tumor

mutation burden (TMB) in patients (pts) with mismatch repair

decient and procient (dMMR and MMRp) tumors in the

GARNET trial

Arndt Vogel1; Thierry André2; Susana Banerjee3; Dominique Berton4;

SusanL. Ellard5; Begoña Jimenez6; Vanessa Samouelian7; Lucy Gilbert8;

Valentina Boni9; Xinwei Han10; Grace Antony11; Jennifer Veneris10;

AnaOaknin12

1Leitender Oberarzt der Klinik für Gastroenterologie, Hepatologie,

Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland,

2Sorbonne University and Saint-Antoine Hospital, Paris, Frankreich

3The Royal Marsden NHS Foundation Trust and Institute of Cancer Research,

London, Vereinigtes Königreich

4GINECO & Institut de Cancerologie de l’Ouest

5BC Cancer–Kelowna, Kelowna, Kanada

6Hospital Clínico Universitario Virgen de la Victoria, Malaga, Spanien

7Centre Hospitalier de l’Université de Montréal, Montréal, Kanada

8McGill University Health Centre, Montréal, Kanada

9Hospital Universitario HM Sanchinarro [Aliation at the time of study, current

aliation Universitario Quironsalud], Madrid, Spanien

10GlaxoSmithKline, Waltham, MA, USA

11GlaxoSmithKline, London, UK

12Vall d’Hebron University Hospital, Barcelona, Spanien

Background: We report a post-hoc analysis of antitumor activity by pro-

grammed death-ligand 1 (PD-L1) expression and TMB in pts with dMMR

and MMRp advanced/recurrent (A/R) solid tumors, assessed in the

GARNET (NCT02715284) Phase I, multicenter, open-label, single-arm

study of PD-1 inhibitor dostarlimab.

Methods: 3 cohorts enrolled pts based on MMR status: dMMR (A1)

and MMRp (A2) A/R EC, and dMMR non-EC solid tumors (F). Pts

received dostarlimab 500 mg IV Q3W for 4 cycles, then 1000 mg IV Q6W

until progression/discontinuation. Exploratory biomarkers were TMB

(Foundation One test; high [TMB-H] ≥10 mutations/Mb) and PD-L1

(combined positive score [CPS] by Ventana assay; high [PD-L1-H]: CPS

≥1). Study not powered to assess antitumor activity within subgroups.

Result: TMB-H and PD-L1-H were common in dMMR solid tumors

(164/209 [78.5%] and 108/209 [51.7%], respectively); PD-L1-H was

observed in 39.4% (56/142) of MMRp EC tumors. Objective response

rate (ORR) (95% CI), per RECIST v1.1 assessed by blinded independent

central review, was higher in pts with TMB-H/PD-L1-H tumors (n=99;

55.6% [45.2–65.5]) than pts with TMB-low (L)/PD-L1-L tumors (n=51;

7.8% [2.2–18.9], respectively), or pts with TMB-L/PD-L1-H (n=57; 17.5%

[8.7–29.9]) or TMB-H/PD-L1-L tumors (n=32; 25% [11.5–43.4]). ORR

(95% CI) was 44.7% (34.9–54.8), 38.7% (29.4–48.6), and 13.4% (8.3–20.1)

for Cohorts A1, F and A2, respectively. Safety previously reported.1

Discussion: -

Conclusion: PD-L1-H and TMB-H were frequently observed in dMMR

cohorts, regardless of tumor type. PD-L1-H was also prevalent in MMRp

EC tumors. Although not powered to assess antitumor activity, ORR was

higher in pts with TMB-H and PD-L1-H solid tumors. Across cohorts,

dMMR status was predictive of response.

Indication of source: GSK 213346. Editorial support provided by

Fishawack Health, funded by GSK. Abstract originally presented at

AACR; New Orleans, LA; Apr 8–13, 2022 (#5135) and published in AACR

Proceedings. Reused with permission. Presented on behalf of the original

authors with permission.

Reference:

Andre T et al. Ann Oncol 2021;32(suppl 5):S829–S866.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1035

The prognostic signicance of PDL-1 on circulating tumor cells

in gastrointestinal tumors

Leonie Konczalla1,2; Leon Kusterer1; Anna Wöstemeier3; Sabine Riethdorf4;

Nathaniel Melling1; Klaus Pantel4; Jakob Izbicki1; Matthias Reeh1

1University Medical Center Hamburg-Eppendorf, Departement of General,

Visceral and Thoracic Surgery, Hamburg, Deutschland

2University Medical Center Hamburg-Eppendorf, Mildred Scheel

Nachwuchszentrum, HaTriCS4, Hamburg, Deutschland

3University Hospital Bonn, General, Visceral-, Thoracic and Vascular Surgery,

Bonn, Deutschland

4University Medical Center Hamburg-Eppendorf, Tumor Biology, Hamburg,

Deutschland

Background: Individual cancer cells can escape from the primary tumor

to the bloodstream, where many immune cells are present. To date, the

immune escape mechanisms of these circulating tumor cells (CTCs) are

poorly understood, but there is an urgent need since exploring the key

mechanisms of CTC surveillance may lead to new therapeutic strategies

to prevent cancer cell proliferation, metastasis, and tumor recurrence.

We hypothesize that one mechanism is the expression of co-inhibitory

receptors such as PDL-1, which lead to decreased immune cell activity

and thereby immune escape of CTCs.

Methods: CTC detection by CellSearch and PBMC characterization by

multiparametric FACS analysis of 81 GI cancer patients with dierent

TMN stage.

Result: In total, 17,28% of all screened patients, CTCs were detected and

35,71% of the CTCs showed robust PDL-1 expression. Interestingly, all

of the PDL-1+ CTC patients appeared with distant metastases or local

recurrence, while patients with PDL-1- CTCs showed smaller frequency

of had distant metastases with only 44,4%. However, PDL-1+ CTC patients

occur to have higher frequency of PBMCs with especially signicantly

upregulated frequency of regulatory T cells (TREG). Moreover, we could

detect a higher expression of PD-1 on cytotoxic CD8+ T cells and tumor

fosteringTREG.

Discussion: Expression of PDL-1 on CTCs appears as a prognostic marker

for enhanced metastasis and thereby reduced outcome. is could be

explained by a PDL-1/PD-1 mediated tumor escape of CTCs in the blood

stream. Whether the expression con PDL-1 on CTCs and primary cancer

and metastasis tissue needs further investigation. However, addressing the

PDL-1/PD-1 axis by immunotherapy could help to reduce CTCs and their

metastatic potential.

Conclusion: PDL-1+ CTCs can be used as prognostic marker in GI can-

cer patients. Furthermore, immunotherapies may be able to reduce the

metastases in these patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 17

1052

Neurolament als Biomarker für sensorische Störungen

beiPatienten unter Chemotherapie

Clara Kalweit1; Tobias Bleumer1; Wolfgang Böhmerle2,3;

SebastianStintzing1; Lars Uwe Stephan1; Uwe Pelzer1

1Department of Hematology, Oncology and Tumorimmunology, Charité

Campus Mitte, Charité - Universitätsmedizin Berlin, Corporate Member of Freie

Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health,

Berlin, Deutschland

2Charité - Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt Universität zu Berlin, NeuroCure Cluster of Excellence,

Berlin

3Department of Neurology, Charité Campus Mitte, Charité - Universitätsmedizin

Berlin, Corporate Member of Freie Universität Berlin, Humboldt- Universität zu

Berlin, and Berlin Institute of Health

Purpose: Polyneuropathies are common side eects in pts undergoing

polychemotherapy with signicant impact on pts’ quality of life. e axo-

nal structural protein neurolament is released in the context of neurode-

generative processes. e aim of the study is to evaluate the neurolament

as a biomarker for sensory disorders.

Methods: At the end of data collection, 100 pts with gastroenterological

cancer and lymphomas will be enrolled in our prospective trial. Pts will

have blood drawn prior to initiation, during and aer therapy, and at 6

and 12 months follow-up. In parallel, nerve conduction velocity (ENG) at

the peroneal nerve will be measured. To detect objectively neuropathies.

In order to record subjectively describe neuropathies, we check at each

examination appointment the quality of life using a modied question-

naire EORTC-QLQC30.

Results: As of April 2022, 51 out of 100 pts have been investigated.

Initially, the mean value of pts without carcinomatous meningitis for the

neurolament was 23,03 pg/ml. For the second examination date, 23 pts

have been included, the mean value was 49,67 pg/ml. 6 pts were examined

a 3rd time, the mean value was 47,2 pg/ml. In parallel, there is an increase

in the TNSr score in ENG from 1.7 points to 6.3 points from the rst to the

3rd examination. Initially, 6 pts already described par- and dysesthesias

in hands and feet. At the 2nd appointment, 22 pts reported moderate to

severe parand dysesthesias in hands and feet. 10 pts still reported tingling,

numbness, and insensations in the hands and feet at the 3rd examination.

Full recruitment is expected in September 2022.

Conclusion: Our study underlines the relevance of early diagnosis of

polyneuropathies as 22 of 51 pts develop moderate to severe paresthesias

and dysesthesias under polychemotherapy. At this point we are not able to

predict signicances regarding the potential biomarker. Now, the data are

not robust enough to perform subgroup analysis. In perspective, however,

the ability to predict polyneuropathies using neurolament will increase

as the amount of data increases.

Disclosure Statement: e authors declare no conict of interest.

1053

Patterns of trophoblast cell surface antigen 2 (TROP2) and

epithelial cell adhesion molecule (EPCAM) expression in

human tumors: A tissue microarray study on 14,766 tumors

Claudia Hube-Magg; David Dum; Ronald Simon; Elena Bady;

TimMandelkow; Maximilian Lennartz; Guido Sauter; Sarah Minner;

Andreas M. Lübke

Universitätsklinikum Hamburg-Eppendorf, Pathologie, Hamburg, Deutschland

Background: Trophoblast cell surface antigen 2 (TROP2) and epithelial

cell adhesion molecule (EPCAM) are cell surface receptors that play a role

in growth signal transduction and cell adhesion. Antibody drug conju-

gates against both proteins are approved or under development.

Methods: To comprehensively study expression patterns of TROP2 and

EPCAM in tumors, a tissue microarray containing 14’766 samples from

120 dierent tumor types was analyzed by immunohistochemistry.

Result: TROP2 positivity was found in 88 of 120 tumor categories, includ-

ing 73 of 76 epithelial tumor types. Particularly high rates of TROP2

positivity were seen in squamous cell carcinomas of various origins and

various categories of urothelial, breast, prostate, pancreatic, and ovar-

ian cancers (>95% positive). EPCAM positivity was found in 99 of 120

tumor categories, including all 76 epithelial tumor categories. Highest

EPCAM positivity (>95% positive) was seen in small cell lung cancers,

urinary bladder cancers, adenocarcinomas of various organs, and tumors

of the female genital tract. Comparison of TROP2 and EPCAM revealed

co-expression in 84 of 120 tumor types, including 73 of 76 epithelial tumor

categories. Co-expression was most frequent (>95% positive for both

markers) in cancers of the urinary bladder, prostate, pancreas, breast, and

ovary. Exclusive EPCAM positivity was found frequently (>75% EPCAM

positive but TROP2 negative) in various neuroendocrine tumors, testic-

ular cancers, thyroid cancers, and Merkel cell carcinomas. Tumor types

with frequent exclusive expression of TROP2 included of squamous cell

carcinomas of various origins.

Conclusion: TROP2 and EPCAM are abundantly co-expressed in a broad

range of epithelial neoplasms, but exclusively expressed in individual

tumor types. Anti-TROP2 cancer drugs and future anti-EPCAM drugs

may be applicable to a broad range of tumor entities.

Disclosure Statement: e authors declare the following: Antibodies for TROP2

and EPCAM were provided from MS Validated Antibodies GmbH (owned by a

family member of GS).

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts18

Breast Cancer

Best-of-Abstract-Vortrag

114

Outcome of breast cancer patients with low hormone receptor

positivity: Analysis of a 15-year population-based cohort

Simone Schrodi1; Michael Braun2; Anne Andrulat2; Nadia Harbeck3;

SvenMahner4; Marion Kiechle5; Evelyn Klein5; Andreas Schnelzer6;

Christian Schindlbeck4,7; Ingo Bauerfeind8; Gabriele Schubert-Fritschle1;

Valentina Nekljudova9; Doris Mayr10; Wilko Weichert11; Carsten Denkert12;

Sibylle Loibl9,13; Jutta Engel1

1Tumorregister München (TRM), Regionalzentrum München, Bayerisches

Krebsregister, Institut für Medizinische Informationsverarbeitung, Biometrie und

Epidemiologie (IBE), Ludwig-Maximilians Universität, München, Deutschland

2Interdisziplinäres Brustzentrum, Rotkreuzklinikum München, München,

Deutschland

3Frauenklinik der Universität München, Brustzentrum, München, Deutschland

4Frauenklinik der Universität München, München, Deutschland

5Frauenklinik rechts der Isar der Technischen Universität München (TUM),

Brustzentrum, München, Deutschland

6Brustzentrum am RoMed Klinikum Rosenheim, Rosenheim, Deutschland

7Frauenklinik Südostbayern, Brustzentrum, Traunstein, Deutschland

8Frauenklinik am Klinikum Landshut, Brustzentrum, Landshut, Deutschland

9German Breast Group (GBG Forschungs GmbH), Neu-Isenburg, Deutschland

10Pathologisches Institut der Ludwigs-Maximilians-Universität München,

München, Deutschland

11Institut für Pathologie an der Technischen Universität München (TUM),

München, Deutschland

12Institut für Pathologie der Philipps-Universität Marburg (UKGM), Marburg,

Deutschland

13Centrum für Hämatologie und Onkologie Bethanien, Frankfurt, Deutschland

Purpose: Guideline recommendations for treatment of breast cancer with

low hormone receptor (HR) expression (1-9%) are ambiguous and several

studies showed more similarities with HR negative tumors than with HR

strongly positive tumors (≥10%). We used a population-based 15-year

cohort to compare patient characteristics and outcome of HR low positive

tumors with HR negative and HR strongly positive tumors, respectively.

Methods: A total of 38,560 women diagnosed with early invasive breast

cancer between 2004 and 2018 within the scope of the Munich Cancer

Registry (MCR) with 4.9 million inhabitants were included. Descriptive

analyses of prognostic factors, treatment, and outcome-analyses using the

Kaplan-Meier method, cumulative incidence in consideration of com-

peting risks, and multivariate analyses (Cox-regression and Fine-Gray

model) were conducted.

Results: 861 patients (2%) had HR low positive, 4862 (13%) HR negative

and 32,837 (85%) HR strongly positive tumors. Within the HER2 negative

cohort (n=33,366), survival of HR low positive tumors was signicantly

worse than that of HR strongly positive tumors (OS hazard ratio 0.66

[0.55-0.78], whereas between HR low positive and HR negative tumors

no signicant survival dierence could be detected (OS hazard ratio 0.93

[0.78-1.11]). e analyses for time to local recurrence, time to lymph node

recurrence, and time to metastasis showed similar results. In contrast,

within the HER2 positive cohort (n=5194), no statistically signicant dif-

ferences between the three HR groups could be detected in the multivar-

iate analyses. Irrespective of HER2 status, patients with low HR positive

tumors seem not to benet signicantly from endocrine therapy.

Discussion: Current denitions for HR positivity and its clinical rele-

vance should be reconsidered.

Conclusion: Patients with HR low positive/HER2 negative tumors could

be regarded and treated similarly to patients with triple-negative tumors.

Prior presentation: is abstract was also presented at the Senologie

Kongress 2021 and is submitted to a peer reviewed journal.

Disclosure Statement: e authors declare no conict of interest.

Poster

Recommendation of the AGO Breast Committee for

HER2-Positive Breast Cancer – Real World Data

onImplementation and Adherence

Wolfgang Janni1; Volkmar Müller2; Jörg Schilling3; Patrik Lindenmaier4;

Andreas Jaeger4

1Universitätsklinikum Ulm - Klinik für Frauenheilkunde und Geburtshilfe, Ulm,

Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für

Gynäkologie, Hamburg, Deutschland

3Gemeinschaftspraxis Dr. med. Schilling, Dr. med. Till, Dr. med. Kohn, Berlin,

Deutschland

4MMF-Marktforschung GmbH, Dortmund, Deutschland

Background: AGO recommendations reect the standard of care for

diagnostics, therapy and surveillance for both EBC and MBC, and are

updated every year. Our nationwide biennial QA initiative analyzes their

implementation in real-world treatment in Germany.

Methods: We collected data on the care structure of gynecological and

oncological centers (2018: n=309, 2020: n=303). Based on this, data on

diagnosis, current therapy and therapy history of patients with HER2-

positive early (EBC; 2018: n=253, 2020: n=253) and metastatic (MBC;

2018: n=415, 2020: n=451) breast cancer were collected representatively

for all treatment facilities in Germany.

Result: EBC: NACT and antibody therapy with pertuzumab (Pz) and tras-

tuzumab (Tz) (dual HER2 blockade; db) was given in 66% (2018: 58%) of

all patients. Important factors for this are age (RR up to 60 years 1.4 [1.2-

1.6]) and tumor size (RR pT≥2 1.3 [1.1-1.5]). Post-neoadjuvant therapy

with db was 71% (67%) in pN+ and 37% (49%) in pN0. In the adjuvant

setting, the share of db in pN+ was 54% (67%), in pN0 31% (44%). T-DM1

aer NACT was administered in 22%. MBC: 72% (71%) of patients did

not receive HER2 targeted pre-treatment before metastasis. Over all lines

of therapy, patients without HER2 targeted pre-treatment received db with

chemotherapy in 83% (74%), patients with Tz pre-treatment received db

in 59% (53%), and T-DM1 in 25% (27%). Patients with db pre- treatment

received T-DM1 in 80% (73%). In 3rd line of therapy or higher, 85% (73%)

received at least two anti-HER2 therapies prior. Db was given with taxane

mono in 82% (75%), Tz without chemotherapy in 53% (56%).

Discussion: NACT with db is established. e addition of Pz in post-

neoadjuvant and adjuvant settings is only partly triggered by node status.

Anti-HER2 therapy is guided by prior therapies, and the sequence “dual

blockade followed by T-DM1” is established.

Conclusion: National recommendations are promptly implemented into

everyday therapy in Germany. Due to the dynamics of available therapy

options, one should continue to dene and review therapy algorithms

( living guidelines).

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 19

Expression of disialoganglioside GD2 in breast cancer

subtypes

Paul Gaß1; Sareetha Kailayangiri2; Hanna Huebner1; Matthias Rübner1;

Arndt Hartmann3; Lothar Häberle1,4; Simon Völkl5; Andreas Mackensen5;

Laura Landgraf3; Rüdiger Schulz-Wendtland6; Nicole Farwick2;

ClaudiaRössig2; Matthias Beckmann1; Peter Andreas Fasching1,7;

RamonaErber3

1Department of Gynecology and Obstetrics, Erlangen University Hospital,

Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of

Erlangen–Nuremberg (FAU), Erlangen, Deutschland

2Department of Pediatric Hematology and Oncology, Münster University

Hospital, Münster, Deutschland

3Institute of Pathology, Erlangen University Hospital, Friedrich Alexander

University of Erlangen–Nuremberg (FAU), Comprehensive Cancer Center

Erlangen-EMN, Erlangen, Deutschland

4Department of Gynecology and Obstetrics, Biostatistics Unit, Erlangen

University Hospital, Friedrich Alex-ander University of Erlangen–Nuremberg

(FAU), Erlangen, Deutschland

5Department of Internal Medicine 5, Hematology/Oncology, Erlangen University

Hospital, Friedrich Alexander University of Erlangen–Nuremberg (FAU),

Comprehensive Cancer Center Erlangen-EMN, Erlangen, Deutschland

6Institute of Diagnostic Radiology, Erlangen University Hospital, Comprehensive

Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen–

Nuremberg (FAU), Erlangen, Deutschland

7Division of Hematology/Oncology, Department of Medicine, David Geen

School of Medicine, Univer-sity of California at Los Angeles, Los Angeles, USA

Background: e disialoganglioside GD2 is a tumor-associated antigen

that may allow targeted immunotherapies (e.g., anti-GD2 antibodies,

GD2 CAR T cells) in patients with neuroblastoma and other solid tumors.

Since GD2 expression has also been reported in subpopulations of breast

cancer patients, this study investigated GD2 expression and its impact on

survival.

Methods: GD2 expression was retrospectively analyzed in a cohort of 894

breast cancer patients, using immunohistochemistry (IHC) and immu-

nouorescence (IF) on tissue microarrays (TMAs). GD2 expression on

IHC (n = 568) and IF (n = 503) was associated with subtypes and patient

outcome.

Result: e highest proportion of GD2-positive tumors was observed

in luminal breast cancer. Signicantly fewer GD2-positive cases were

detected in triple-negative breast cancer (TNBC) compared with other

subtypes. e proportions of GD2-expressing tumors were signicantly

lower in HER2-positive breast cancer in comparison with luminal tumors

on IF staining (but not IHC). GD2 expression on IHC or IF was not sig-

nicantly associated with disease-free or overall survival, either in the

overall cohort or in the individual subtypes.

Discussion: GD2 in breast cancer might be a suitable tumor-associated

antigen that could be targeted on the cell surface in patients with a poor

prognosis according to established clinical and pathological risk factors.

Molecular targeting of pathways associated with GD2 synthesis and

expression would be most eective if GD2 was indeed a marker of aggres-

sive and/or tumor-initiating cells, with critical contributions to tumor

growth and metastasis.

Conclusion: GD2 expression can be found in more than 50 % of breast

cancer tumors, with the highest frequency in hormone receptor–positive

tumors. No correlations between GD2 expression and prognosis were

observed. Patients with GD2-positive advanced breast cancer of all sub-

types may benet from GD2-targeting immunotherapies, which are cur-

rently undergoing clinical testing.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

Interim analysis (n=150) of the multi-national, prospective,

non-interventional ELEANOR study observing real-life

extended adjuvant treatment with neratinib in patients with

HER2+ / HR+ early breast cancer (eBC)

Diana Lüftner1; Rupert Bartsch2; Urs Breitenstein3; Marija Balic4;

ChristianJackisch5; Volkmar Müller6; Gabriel Rinnerthaler7;

MarcusSchmidt8; Michael Schwitter9; Khalil Zaman10; Denise Wrobel11;

Dagmar Guth12; JürgenTerhaag13; Matthias Zaiss14; Andrea Distelrath15;

Andreas Lorenz16; TimoSchinköthe17; Nadia Harbeck18

1University Hospital Charité, Berlin, Deutschland

2Medical University of Vienna, Department of Medicine I, Division of Oncology,

Vienna, Österreich

3Brust-Zentrum Zürich, Divison of Oncology, Zurich, Schweiz

4Medical University Graz, Department of Internal Medicine, Divison of Oncology,

Graz, Österreich

5Klinikum Oenbach, Department of Gynecology and Obstetrics, Oenbach,

Deutschland

6University Hospital Hamburg-Eppendorf, Department of Gynecology and

Obstetrics, Hamburg, Deutschland

7Paracelsus Medical University, Department of Internal Medicine III with

Haematology, Medical Oncology, Haemostaseology, In-fectiology and

Rheumatology, Oncologic Center, Salzburg Cancer Research Institute –

Laboratory for Immunological and Mo-lecular Cancer Research (SCRI-LIMCR),

Salzburg, Österreich

8University Hospital Mainz, Dept. Gynecology, Mainz, Deutschland

9Kantonsspital Graubünden, Chur, Schweiz

10Lausanne University Hospital CHUV, Breast Center, Lausanne, Schweiz

11Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland

12Gynäko-onkologische Praxis Dr. Guth, Plauen, Deutschland

13Rottal/Inn Clinic, Eggenfelden, Deutschland

14Praxis für interdisziplinaere Onkologie, Freiburg, Deutschland

15Praxisgemeinschaft Onkologie und Urologie, Wilhelmshaven, Deutschland

16Gynäko-onkologische Praxis Dr. Lorenz, Hildburghausen, Deutschland

17CANKADO Service GmbH, Kirchheim, Deutschland

18LMU University Hospital Munich, Breast Center, Dept. OB&GYN, Munich,

Deutschland

Background: Neratinib is registered in Europe as extended adjuvant treat-

ment for adult patients with Human Epidermal Growth Factor Receptor

2-positive (HER2+) and Hormone receptor-positive (HR+) eBC within

one year aer completed adjuvant trastuzumab-based therapy (“EMA-/

Swissmedic-label” population). In the ExteNET trial, extended adjuvant

neratinib improved the absolute 5-year invasive disease-free survival rate

by 5.1% vs. placebo in this population (90.8% vs. 85.7%; HR 0.58 [95%

CI 0.41-0.82])1. In the absence of primary prophylaxis, grade 3 diarrhea

occurred in 39% of patients in the ExteNET trial.1 ELEANOR is the rst

study to investigate real-world use of neratinib and its management in

eBC patients in Germany, Austria and Switzerland.

Methods: 300 patients will be enrolled in accordance with the specica-

tions of the local Summary of Product Characteristics. Primary objective

is adherence to neratinib treatment (i.e., proportion of patients with nera-

tinib intake for ≥75% of treatment days). Secondary objectives include

analysis of prior trastuzumab-based therapies (including pertuzumab and

T-DM1), neratinib dosing and management, relapses, safety / tolerability,

and quality of life (using the CANKADO eHealth application).

Result: Between July 2020 and April 2022, 228 patients were enrolled at 61

sites; patient enrollment is ongoing. We will present baseline demograph-

ics, tumor characteristics, prior treatments and neratinib safety/tolerabil-

ity for the rst 150 enrolled patients (interim analysis, data cut Nov 2021).

Discussion: is analysis presents a snapshot of the current treatment

landscape and real-life neratinib use.

Conclusion: ELEANOR will help to characterize the use of extended adju-

vant HER2-targeted therapy in the current treatment landscape focusing

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts20

on neratinib management aer dierent prior therapies. e study is

funded by Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre

Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil,

Switzerland).

Reference:

1. Chan A et al. Clin Breast Cancer 2021;21(1):80–91.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

Recommendation of the AGO Breast Committee for

Triple-Negative Breast Cancer – Real World Data

onImplementation and Adherence

Christian Jackisch1; Wolfgang Janni1; Volkmar Müller2; Jörg Schilling3;

Patrik Lindenmaier4; Andreas Jaeger4

1Universitätsklinikum Ulm - Klinik für Frauenheilkunde und Geburtshilfe,

Ulm, Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für

Gynäkologie, Hamburg, Deutschland

3Gemeinschaftspraxis Dr. med. Schilling, Dr. med. Till, Dr. med. Kohn, Berlin,

Deutschland

4MMF-Marktforschung GmbH, Dortmund, Deutschland

Background: New biomarker-dependent options in therapy for tri-

ple-negative breast cancer (TNBC) are reected in AGO guidelines and

therapy algorithms. Our nationwide biennial QA initiative analyzes their

implementation in real-world treatment in Germany.

Methods: We collected data on the care structure of gynecological and

oncological centers (2018: n=309, 2020: n=303). On this basis, data on

diagnosis, current therapy and therapy history of patients with early

(eTNBC; 2018: n=153, 2020: n=180) and metastatic (mTNBC; 2018:

n=200, 2020: n=205) TNBC were collected representatively for all treat-

ment facilities in Germany.

Result: eTNBC: In 2020, testing for gBRCA mutation was performed in

78% (2018: N/A) of patients up to 60 years of age. NACT was performed

in 86% (78%). A platinum salt was added in 80% (55%) of patients in

the NACT setting and in 65% (32%) in the adjuvant setting. Dose-dense

chemotherapy with anthracycline and taxane was used in 58% (47%) of all

cases. mTNBC: gBRCA testing was performed in 47% (31%) of patients.

PD-L1 expression was measured in 71% (6%) of patients. In PDL1positive

patients, 78% received a PD-L1 inhibitor. In PD-L1 negative patients, 45%

(37%) experienced mono-chemotherapy, 33% (38%) combinations with

VEGFi, and 15% (20%) combinations with platinum. Qualifying patients

received PARPi in 71% (18%).

Discussion: NACT is established, as is the administration of platinum

derivatives and taxanes. Dose-dense regimens are frequently used over

conventional ones, and their importance may increase. In mTNBC,

PD-L1 testing is performed in the majority of patients, while BRCA test-

ing is performed in only half. Immunotherapy and PARP inhibition are

the preferred options in qualifying patients. For the majority of mTNBC

patients, however, treatment options remain unchanged.

Conclusion: AGO recommendations for biomarker testing are promptly

implemented into everyday therapy in Germany. Due to the dynamics of

the available therapy options, one should continue to dene and review

quality indicators.

Disclosure Statement: e authors declare no conict of interest.

120

Knockdown of AKT3 activates HER2 and DDR kinases in

bone-seeking breast cancer cells, promotes metastasis

in vivo and attenuates the TGF/CTGF Axis

Nico Hinz1; Anke Baranowsky2; Michael Horn3; Malte Kriegs4;

FreyaSibbertsen1; Daniel Smit1; Philippe Clezardin5; Tobias Lange6;

Thorsten Schinke2; Manfred Jücker1

1Institute of Biochemistry and Signal Transduction, University Medical Center

Hamburg Eppendorf, Hamburg, Deutschland

2Department of Osteology and Biomechanics, University Medical Center

Hamburg Eppendorf, Hamburg, Deutschland

3University Cancer Center Hamburg, University Medical Center Hamburg

Eppendorf, Hamburg, Deutschland

4Department of Radiotherapy & Radiation Oncology, University Medical Center

Hamburg Eppendorf, Hamburg, Deutschland

5Research Unit UMR S1033, INSERM, Lyon, Frankreich

6Department of Anatomy and Experimental Morphology, University Medical

Center Hamburg Eppendorf, Hamburg, Deutschland

Background: Bone metastases frequently occur in breast cancer patients

and lack appropriate treatment options. Understanding the molecu-

lar mechanisms involved in the multistep process of breast cancer bone

metastasis and tumor-induced osteolysis is of paramount interest. e

serine/threonine kinase AKT plays a crucial role in breast cancer bone

metastasis but the eect of individual AKT isoforms remains unclear.

Methods: AKT isoform-specic knockdowns were generated in the

bone-seeking MDA-MB-231 BO subline and the eect on proliferation,

migration, invasion, and chemotaxis was analyzed by live-cell imaging.

Kinome proling and Western blot analysis of the TGF/CTGF axis were

conducted and metastasis was evaluated by intracardiac inoculation of

tumor cells into NOD scid gamma (NSG) mice.

Result: MDA-MB-231 BO cells exhibited an elevated AKT3 kinase

activity in vitro and responded to combined treatment with AKT- and

mTOR-inhibitors. Knockdown of AKT3 signicantly increased migra-

tion, invasion, and chemotaxis in vitro and metastasis to bone but did

not signicantly enhance osteolysis. Furthermore, knockdown of AKT3

increased the activity of pro-metastatic HER2 and DDR1/2 but low-

ered protein levels of CTGF aer TGF-stimulation, an axis involved in

tumor-induced osteolysis.

Discussion: Our data indicate that the three AKT isoforms are dieren-

tially involved in the regulation of breast cancer metastasis. We demon-

strate that knockdown of AKT3 in MDA-MB-231 BO cells resulted in an

enhanced metastasis to the bone in NSG mice. In addition, we demon-

strate that the combined treatment with AKT and mTOR inhibitors syner-

gistically inhibited proliferation and migration of MDA-MB-231 BO cells.

Conclusion: We demonstrate that knockdown of AKT3 in bone-seeking

breast cancer cells promotes metastasis to the bone. On the basis of our

data, the treatment of triple negative breast cancer in a non-metastatic

stage with an AKT1/2 inhibitor in combination with mTOR inhibitors

should be analyzed in further studies.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 21

127

Process evaluation of an intensied patient-reported outcome

monitoring study with metastatic breast cancer patients

Clara Breidenbach1; Christoph Kowalski1; Anna Maria Hage2;

TheresePross2; Friedrich Kühn2; Maria Margarete Karsten2

1Deutsche Krebsgesellschaft e. V., Berlin, Deutschland

2Charité Universitaetsmedizin Berlin, Department of Gynecology,

Berlin,Deutschland

Background: Treating metastatic breast cancer patients represents a chal-

lenge from a medical, psychosocial and economical point of view for the

entire clinical team. Earlier research has shown that an intensied mon-

itoring with patient-reported outcomes (PROs) can improve metastatic

cancer patients’ quality of live and survival. e aim of the randomized

multicentric PRO B study is to investigate if those positive eects are

also applicable to metastatic breast cancer patients in the German health

care system. In case of positive results, the PRO monitoring should be

transferred to routine care. erefore, an integrated process evaluation is

planned during the study. It aims to answer whether the intervention is

feasible in everyday clinical practice as well as whether implementation is

center (“context”) dependent.

Methods: Online surveys with all study sites will be conducted at several

time points during the intervention phase of the study (May 2021 – May

2023) to generate a general overview of the acceptance, satisfaction and

outreach of the intervention among health professionals. Furthermore,

semi-structured interviews with health professionals from high perform-

ing (with regard to recruitment) as well as from lower performing study

sites will be performed at several time points to gain a deeper understand-

ing of barriers and facilitators for intervention adherence. e interview

guide will be inspired by the Normalisation Process eory.

Result: First results will be available at the time of the congress.

Discussion: e process evaluation embedded in the PRO B study may

help to assess the feasibility, acceptance and quality of the intervention

and thus provide insights for its implementation. In addition, process

evaluation can be used to identify causal mechanisms and how context

inuences the results of the intervention study.

Conclusion: Process evaluation will provide recommendations for the

implementation of intensied PRO monitoring in breast cancer centers

in Germany.

Disclosure Statement: e authors declare the following: Clara Breidenbach and

Christoph Kowalski are employees of the German Cancer Society, one of the two

bodies responsible for the certication of breast cancer centers.

157

Association between mammographic breast density and

achievement of a pathologic complete remission (pCR)

after neoadjuvant chemotherapy (NACT) for early breast

cancer (EBC)

Mohamed Shaheen1; Cornelia Kolberg-Liedtke2; Oliver Homann2;

Ann-Kathrin Bittner2; Sarah Wetzig3; Miltiades Stephanou1;

Hans-Christian Kolberg1

1Marienhospital Bottrop, Klinik für Gynäkologie und Geburtshilfe, Bottrop,

Deutschland

2Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen,

Deutschland

3Marienkrankenhaus Schwerte, Brustzentrum, Schwerte, Deutschland

Background: Achievement of pathologic complete remission (pCR) aer

NACT is indicating an improved prognosis. An association between pCR

and mammographic breast density as dened by BIRADS (Breast Imaging

Reporting and Data System) could be demonstrated. However, the de-

nition of mammographic breast density by the American College of

Radiology (ACR) is widely used worldwide and data regarding an associ-

ation of breast density by this denition and pCR aer NACT are missing.

Methods: We conducted a retrospective analysis among patients who had

received neoadjuvant chemotherapy (NACT) for EBC. An association

between mammographic breast density (ACR) and pCR was analyzed.

Result: 185 patients were included in this analysis, 35.7% of whom

achieved a pCR. Mammographic breast density was ACR 1 in 15.1%, ACR

2 in 41.6%, ACR3 in 38.4% and ACR 4 in 4.9% of the patients. A negative

correlation between mammographic breast density and pCR (correlation

coecient (CC) -0.240)(p=0.001) and the association of decreasing pCR

rates with increasing mammographic breast density (pCR rates by ACR 1:

53.6%, ACR 2: 41.6%, ACR 3: 25.4% and ACR 4: 11.1 %)(p=0.013) were

statistically signicant. ese results were independent of age, ER status,

PR status, HER2neu status and grading.

Conclusion: In our retrospective analysis higher mammographic breast

density as dened by ACR was signicantly correlated with a lower chance

of achieving a pCR aer NACT. e pathophysiological cause of this asso-

ciation should be further investigated to reveal potential mechanisms of

treatment resistance.

Disclosure Statement: e authors declare no conict of interest.

161

Benets and risks of patient participation in multidisciplinary

tumor conferences in breast cancer: main ndings of the

mixed methods PINTU study

Lena Ansmann1; Christian Heuser2; Annika Diekmann2;

BarbaraSchellenberger2; Nicole Ernstmann2

1Abteilung für Organisationsbezogene Versorgungsforschung, University of

Oldenburg, School of Medicine and Health Sciences, Oldenburg, Deutschland

2Forschungsstelle für Gesundheitskommunikation und Versorgungsforschung,

Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,

Universitätsklinikum Bonn, Bonn, Deutschland

Background: Research in breast cancer centers in Germany revealed that

between 5-7% of patients have participated in multidisciplinary tumor

conferences (MTCs) during their own case discussion. Research on the

risks and benets is rare. e PINTU study aimed to answer the follow-

ing research questions: How do providers perceive patient participation

in MTCs with regard to feasibility and quality of decision-making? In

how far do MTCs with and without patient participation dier? How do

patients experience participation and how does it aect PROs?

Methods: In an exploratory, observational, prospective multicenter study,

MTCs with/without patient participation in 6 breast and gynecological

cancer centers in NRW were examined. First, n=32 interviews with pro-

viders were carried out. Second, video/audiotaped observations in MTCs

were conducted (n=317, n=95 patients with and n=222 without partici-

pation). ird, patients with/without participation were surveyed before

(T0), directly aer MTC (T1) and 4 weeks aer MTC (T2). Survey data

were analyzed by descriptive and multivariate statistics using propensity

scores.

Result: (1) e way patient participation is implemented varied strongly

by center. (2) Case discussions with patients present may not be feasible in

routine care. (3) Most patients experienced patient participation in MTC

as positive, whereas some reported negative experiences. (4) Providers

reported a mixed picture of positive and negative experiences as well. (5)

Shared decision making in MTCs seemed dicult under the current cir-

cumstances. (6) e development of fear of cancer progression, unmet

information needs and quality of life did not show substantial dierences

by MTC participation.

Discussion: Although numbers of patients and centers are limited, this is

the largest study to date on this controversial topic.

Conclusion: e next urgent questions to be answered before recom-

mendations for or against patient participation in MTCs can be made are:

Which patients could benet? How can MTC participation be arranged

for the patient’s benet?

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts22

186

Reduction of the ablation rate through oncoplastic surgery

in breast-conserving therapy for breast cancer -Experience

of a singular breast center

Hala Allakeh; Wladimir Pauker

Rotenburg (Wümme), AGAPLESION Diakonieklinikum Rotenburg, Frauenklinik,

Rotenburg (Wümme), Deutschland

Objective: In cases of an unfavorable relative tumor size or an unfavor-

able tumor location as well as multicentricity and multifocality of a breast

cancer, an oncologically safe excision with a cosmetic result can be carried

out by an oncoplastic operation and the rate of mastectomies can be sig-

nicantly reduced.

Maternal: From December 2019 to July 2021, 273 patients with a pri-

marily histologically conrmed breast cancer were treated surgically, 97

(37.5%) of them with the use of oncoplastic breast reduction techniques.

29 (10.6%) of 273 patients received ablatio mammae or skin sparing mas-

tectomy (SSM) either primarily or as a result of the tumor-involved mar-

gins aer tumor removal. Four categories of breast-conserving operations

were performed: conventional tumorectomy, segment resection with mas-

topexy was ideal for tumors in the upper and lower outer quadrants. A

modied Burow’s triangle advancement ap was used for tumors in the

upper and lower inner quadrants. A round-block reduction technique was

performed for periareolar lesions. For subareolar tumors, the Grisotti ap

technique was used.

Results: e mastectomy rate in retrospective data from 748 patients was

21.6% (162) compared to 10.6% (29) from 273 patients with 37.5% (97)

use of oncoplastic breast reduction techniques.

Discussion: e use of oncoplastic technology in modern senology can

signicantly reduce the mastectomy rate.

To summarize: e oncoplastic breast reduction techniques enable large-

scale excisions to be carried out with good oncological safety as well as

deliver positive cosmetic results and can be used as an alternative to mas-

tectomy in large carcinomas. ere is very limited evidence of oncological

outcomes of breast-conserving surgery for these large tumors.

Disclosure Statement: e authors declare no conict of interest.

190

Heterogeneity between core needle biopsy and primary

tumor tissue in early breast cancer patients: Comparison of

intrinsic subtypes after dierent treatment regimes

Laura Weydandt1; Anne Kreklau1; Ivonne Nel1; Lars-Christian Horn2;

Bahriye Aktas1

1Universitätsklinikum Leipzig, Klinik und Poliklinik für Frauenheilkunde,

Leipzig, Deutschland

2Universitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Deutschland

Background: All initial therapeutic decisions in early breast cancer are

commonly based on the expression proles of estrogen (ER), progesterone

(PR) and the human epidermal growth factor 2 (HER2) receptors. Only

little data is known about receptor changes aer upfront therapy. Here, we

compared receptor expression proles between core needle biopsy (CNB)

tissue and primary tumor tissue aer dierent treatment regimes.

Methods: In a German single center study, we retrospectively analyzed

248 breast cancer patients during primary treatment regime between 2014

and 2020. Patients had either neoadjuvant chemotherapy, neoadjuvant

endocrine therapy or no upfront therapy. Tumor material was obtained

by core needle biopsy (CNB) at primary diagnosis and during primary

oncological surgery of the axilla and breast. Analysis of histological sub-

type, grading, Ki67 index and expression proling of ER, PR, HER2, was

performed using formalin-xed, paran-embedded (FFPE) specimens.

Tumors were grouped into dierent intrinsic subtypes according to the

international St. Gallen classication in either Luminal A, Luminal B,

HER2-enriched or triple negative.

Result: Overall, 77 (36%) patients had an intrinsic subtype change

between CNB and denitive surgical treatment, 139 (64 %) patients had

no subtype change. ere were 44 (52%) changes aer neoadjuvant che-

motherapy, 17 (35%) changes aer neoadjuvant endocrine therapy and 16

(20%) subtype changes aer no upfront therapy (p<0.0001 for the eect of

neoadjuvant chemotherapy).

Discussion: Our results imply the high frequency of intrinsic subtype

changes aer neoadjuvant therapy. Subtype changes should be taken into

account for an optimal and individual treatment.

Conclusion: Further research needs to be conducted to investigate

whether an individual treatment decision based on the receptor prole

aer primary treatment might improve clinical outcome of breast cancer

patients.

Disclosure Statement: e authors declare no conict of interest.

210

An open-label, multinational, multicenter, phase 3b/4 study

of trastuzumab deruxtecan (T-DXd) in patients with or without

baseline brain metastasis with previously treated advanced/

metastatic human epidermal growth factor receptor

2-positive breast cancer (HER2+ BC): DESTINY-Breast12

Volkmar Müller1; Nancy U. Lin2; Eva Ciruelos3; Guy Jerusalem4;

Naoki Niikura5; Giuseppe Viale6; Emma Oscroft7; Shawn Anand7;

Graham Walker7; Nadia Harbeck8

1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

2Dana-Farber Cancer Institute, Boston, USA

3University Hospital 12 de Octubre, Madrid, Spanien

4Centre Hospitalier Universitaire du Sart Tilman Liège and Liège University,

Liège, Belgien

5Tokai University School of Medicine, Kanagawa, Japan

6European Institute of Oncology, Milan, Italien

7AstraZeneca Pharmaceuticals, Gaithersburg, USA

8Breast Center, LMU University Hospital, Munich, Deutschland

Background: HER2+ BC is associated with a high incidence (up to 50%)

of brain metastasis (BM) despite advances in treatment [1]. Although

several agents have been studied in patients (pts) with HER2+ BC with

BM, an unmet need remains due to the poor prognosis in these pts. In

DESTINY-Breast01, T-DXd demonstrated ecacy in the overall popula-

tion and preliminary ecacy in a subgroup of pts with stable BM, with

an objective response rate (ORR) of 61.4% and an extracranial conrmed

ORR by independent central review (ICR) of 58.3%, median progres-

sion-free survival (PFS) of 19.4 mo and 18.1 mo, and median duration

of response (DOR) of 20.8 mo and 16.9 mo, respectively[2, 3]. Here we

describe a trial evaluating T-DXd in pts ± BM with previously treated

advanced/metastatic HER2+ BC.

Methods: DESTINY-Breast12 (NCT04739761) is an open-label, multi-

center, international, phase 3b/4 study assessing the ecacy and safety of

T-DXd 5.4 mg/kg in pts with HER2+ BC ± BM. Pts will be enrolled in 1

of 2 cohorts (250 pts each): cohort 1 (without BM at baseline) and cohort

2 (with BM at baseline). Pts must have previously treated advanced/meta-

static HER2+ BC that has progressed with ≥1 prior anti-HER2–based reg-

imen and received ≤2 lines of therapy in the metastatic setting (excludes

pts with prior tucatinib treatment). Pts with BM must have untreated

BM not needing immediate local therapy or previously treated stable

or progressing BM. Primary endpoints are ORR in cohort 1 and PFS in

cohort 2 (both by RECIST version 1.1 per ICR). Secondary endpoints in

both cohorts are OS, DOR, time to progression, duration of subsequent

therapy, PFS2, safety, and changes in symptoms, functioning, and QOL.

Incidence of new symptomatic BM is a secondary endpoint in cohort 1,

and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and

time to new BM are secondary endpoints in cohort 2.

Result: n/a

Discussion: n/a

Conclusion: n/a

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 23

Indication of source:

1. Freedman, R.A., et al. 2019. 37(13): p. 1081-1089.

2. Modi, S., et al. 2021. 81(4 Supplement): p. PD3-06-PD3-06.

3. Jerusalem, G., et al. Annals of Oncology, 2020. 31: p. S63-S64.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

246

Implementation of new tests and treatments for patients

with advanced triple negative breast cancer in routine

care – data from the registry platform OPAL

Mark-Oliver Zahn1; Anja Welt2; Marc Thill3; Elmar Stickeler4;

Matthias Zaiss5; Arnd Nusch6; Erik Engel7; Marco Chiabudini8;

Lisa Kruggel8; Martina Jänicke8; Norbert Marschner5; Achim Wöckel9;

Nadia Harbeck10; Thomas Decker11

1Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation

Harz, Goslar, Deutschland

2Universitätsklinikum Essen Innere Klinik Tumorforschung, Essen, Deutschland

3Agaplesion Markus Krankenhaus Klinik für Gynäkologie und Gynäkologische

Onkologie, Frankfurt a.M., Deutschland

4Uniklinik RWTH Aachen, Gynäkologie und Geburtsmedizin, Aachen,

Deutschland

5Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br., Deutschland

6Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland

7Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Deutschland

8iOMEDICO, Freiburg i.Br., Deutschland

9Universitätsklinikum Würzburg Frauenklinik und Poliklinik, Würzburg,

Deutschland

10LMU Klinikum München, Brustzentrum, Frauenklinik, München, Deutschland

11Studienzentrum Onkologie Ravensburg Prof. Dr. Dechow, Prof. Dr. Decker,

Dr.Nonnenbroich GbR, Ravensburg, Deutschland

Background: Since 2019, new treatment options for patients (pts) with

advanced triple negative breast cancer (TNBC) have been approved in the

EU: PARP inhibitors for pts with BRCA-mutated and PD-L1 inhibitors

for pts with PD-L1 positive BC. e OPAL registry platform was used to

analyze the implementation of these new tests and treatments into routine

care.

Methods: OPAL (NCT03417115) is a prospective registry that continues

the Tumor Registry Breast Cancer. By March 2022, a total of 3883 pts

with advanced BC had been recruited, of whom 1883 since start of OPAL

(01/2018). Details on all (sequential) treatments, patient and tumor char-

acteristics, biomarker testing, and outcomes are collected. Here data were

analyzed for 254 OPAL pts with TNBC.

Result: Overall, most frequent rst-line regimens since 2018 were (nab)

paclitaxel ±bevacizumab (BEV) (23%), (nab)paclitaxel +atezolizumab

(21%), capecitabine ±BEV (19%), (nab)paclitaxel +carboplatin ±BEV

(10%) and carboplatin +gemcitabine (4%). Second-line (n=98), most

frequent treatments were anthracyclines (18%) and eribulin (17%). Since

2018, the PD-L1 testing rate at start of rst-line treatment has increased

from 14% to 74%. Out of 133 pts tested, 63 pts (47%) had a positive test

result, 53 since the approval of checkpoint-inhibitor atezolizumab (ATZ)

in 08/2019. 41 out of 53 pts (77%) were treated with ATZ rst-line. e

testing rate for BRCA1 or BRCA2 mutations was between 9-14%. Out of

30 pts tested, 3 pts carried a mutation, but no use of PARP-inhibitors was

documented so far in rst-line. Prior to approval of ATZ, median PFS and

OS was 6.4 months (95% CI 5.4-7.3) and 14.9 months (95% CI 12.3-18.4),

respectively. Aer approval of ATZ, the majority of all TNBC pts were still

alive. Updated data will be presented.

Conclusion: Our data show that PD-L1 testing and the new treatment

option for PD-L1 positive tumors were quickly implemented in routine

care. BRCA1/2 testing is performed less oen, especially in rst-line sit-

uation. With longer follow-up, OPAL will show the impact of these new

targeted therapies on the outcome in routine care.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

269

AXSANA – EUBREAST 3 (AXillary Surgery After NeoAdjuvant

Treatment): An international prospective multicenter cohort

study of the EUBREAST study group to evaluate dierent

surgical methods of axillary staging (sentinel lymph node

biopsy, targeted axillary dissection, axillary dissection) in

clinically node-positive breast cancer patients treated with

neoadjuvant chemotherapy (NCT04373655)

Maggie Banys-Paluchowski1,2; Ste Hartmann3; Elmar Stickeler4;

Jana de Boniface5,6; Oreste Gentilini7; Sarah Fröhlich3; Marc Thill8;

Franziska Ruf1; Michael Hauptmann9; Güldeniz Karadeniz Cakmak10;

Isabel Teresa Rubio11; Maria Luisa Gasparri12,13; Michalis Kontos14;

Eduard-Alexandru Bonci15,16; Laura Niinikoski17; Rosa DI Micco7;

Dawid Murawa18; David Pinto19; Florentia Peintinger20,21; Lukas Dostalek22;

Christine Solbach23; Matilda Appelgren5; Jens-Uwe Blohmer24;

Elisabeth Thiemann25; Michael Weigel26; Gabriele Kaltenecker27; Kerstin

Ramaker28; Michael G. Schrauder29; Thorsten Kühn30

1Department of Obstetrics and Gynecology, University Hospital of Schleswig

Holstein, Campus Lübeck, Lübeck, Deutschland

2Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf,

Deutschland

3University Hospital Rostock, Department of Gynecology and Obstetrics,

Rostock, Deutschland

4University Hospital Aachen, Department of Gynecology and Obstetrics, Aachen,

Deutschland

5Karolinska Institutet, Dept. of Molecular Medicine and Surgery, Stockholm,

Schweden

6Capio St. Göran’s Hospital, Dept. of Surgery, Stockholm, Schweden

7San Raaele Hospital Milan, Milano, Italien

8AGAPLESION Markus Krankenhaus, Department of Gynecology and

Gynecological Oncology, Frankfurt am Main, Deutschland

9Brandenburg Medical School Theodor Fontane, Neuruppin, Deutschland

10Zonguldak BEUN The School of Medicine, General Surgery Department, Breast

and Endocrine Unit, Kozlu/Zonguldak, Türkei

11Breast Surgical Unit, Clínica Universidad de Navarra, Madrid, Spanien

12Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale,

Ospedale Regionale di Lugano, Lugano, Schweiz

13University of the Italian Switzerland (USI), Faculty of Biomedicine, Lugano,

Schweiz

141st Department of Surgery, Laiko Hospital, National and Kapodistrian

University of Athens, Athens, Griechenland

15Department of Surgical Oncology, ”Prof. Dr. Ion Chiricuță” Institute of

Oncology, Cluj-Napoca, Rumänien

1611th Department of Oncological Surgery and Gynecological Oncology, “Iuliu

Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Rumänien

17Breast Surgery Unit, Comprehensive Cancer Center, Helsinki University

Hospital, University of Helsinki, Finnland

18Department of General Surgery and Surgical Oncology, Collegium Medicum,

University of Zielona Góra, Zielona Góra, Polen

19Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation,

Lisboa, Portugal

20Institute of Pathology, Medical Univ. Graz, Graz, Österreich

21Department of Gynecology, LKH Leoben, Leoben, Österreich

22Gynecologic Oncology Center, Department of Obstetrics and Gynecology,

First Faculty of Medicine, Charles University, General University Hospital, Prague,

Tschechische Republik

23Breast Center, Department of Gynecology and Obstetrics, University of

Frankfurt, Frankfurt, Deutschland

24Department of Gynecology and Breast Cancer Center, Charité Berlin, Berlin,

Deutschland

25Brustzentrum Osnabrück - Niels-Stensen-Kliniken, Osnabrück, Deutschland

26Leopoldina-Krankenhaus, Schweinfurt, Deutschland

27Städtisches Klinikum Karlsruhe Frauenklinik, Karlsruhe, Deutschland

28Regio Klinikum Pinneberg, Pinneberg, Deutschland

29Klinikum Aschaenburg-Alzenau, Aschaenburg, Deutschland

30Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen,

Deutschland

Background: e optimal surgical staging procedure of the axilla in

patients who convert from a clinically positive to a clinically negative node

status through neoadjuvant chemotherapy is still controversial. Widely

diverse techniques such as Axillary Lymph Node Dissection (ALND),

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts24

Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy

(TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given pref-

erence in dierent international guidelines. So far, no comparative data

on the oncological outcome or the morbidity of the dierent procedures

are available.

Methods: AXSANA is an international prospective cohort study includ-

ing cN+ patients treated with dierent axillary staging techniques. e

study was initiated by the EUBREAST network and funded by AGO-B,

Claudia von Schilling Foundation, Ehmann-Stiung Savognin, AWOgyn,

EndoMag, MeritMedical and Mammotome, and supported by NOGGO

and GBG. Primary aims are invasive disease-free survival, axillary recur-

rence rate and quality of life in cN+ → ycN0 patients treated with dierent

staging techniques. Target accrual is 3000 patients.

Result: So far, 868 cN+ patients from 13 countries were recruited. Median

age was 52 years. Nodes were suspicious upon clinical examination and

imaging in 67% and imaging only in 33% of patients. 24% of patients had

≥4 suspicious lymph nodes. In 58% of cases, ≥1 target node was marked

(1 node in 90%, 2 nodes in 8%, ≥3 nodes in 2%). Clip/coil was used in

79% of patients, followed by carbon ink (12%) and magnetic seed (9%).

70% of patients converted to ycN0. TAD was planned in 43%, ALND in

38%, SLNB in 15% and TLNB in 7% of patients. 61% of study sites choos-

ing TAD reported to have performed ≥30 procedures. Among patients

receiving preoperative target node localization, most (75%) underwent

wire-guided localization.

Discussion: Our preliminary data show that axillary staging is very het-

erogeneous among countries. TAD is widely used despite lack of long-

term oncological data.

Conclusion: Final results of AXSANA will contribute to clarify the onco-

logical safety of axillary surgical de-escalation.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

283

persevERA Breast Cancer (BC): Phase III study evaluating

the ecacy and safety of giredestrant (GDC-9545) +

palbociclib versus letrozole + palbociclib in patients (pts)

with estrogen-receptor-positive, HER2-negative locally

advanced or metastatic BC (ER+/HER2– LA/mBC)

Volkmar Müller1; Nicholas Turner2; Komal Jhaveri3; Aditya Bardia4;

Naoki Niikura5; Véronique Diéras6; Carlos Barrios7; Seock-Ah Im8;

Meritxell Bellet9; Ching-Wei Chang10; Graham Ross11; Monika Patre11;

Sherene Loi12

1Universitätsklinikum Hamburg Eppendorf, Klinik und Poliklinik für Gynäkologie,

Hamburg, Deutschland

2The Royal Marsden Hospital, London, Vereinigtes Königreich

3Memorial Sloan-Kettering Cancer Center, New York, USA

4Mass General Cancer Center, Boston, USA

5Tōkai-Universität, Shibuya City, Japan

6Eugene Marquis Center, Rennes, Frankreich

7Centro de Pesquisa em Oncologia, Porto Alegre, Brasilien

8Seoul National University College of Medicine, Seoul, Republik Korea

9Hospital Universitari Vall d’Hebron, Barcelona, Spanien

10Genentech Inc, South San Francisco, USA

11Homann-La Roche, Basel, Schweiz

12Peter MacCallum Cancer Centre, Melbourne, Australien

Background: Modulating estrogen synthesis and/or ER activity is the

mainstay of treatment for pts with ER+ BC. Despite substantial progress,

many pts experience relapse during/aer adjuvant endocrine therapy.

However, even though resistant to aromatase inhibitors (AIs) or tamox-

ifen, growth and survival of the majority of tumors are thought to remain

dependent on ER signaling. erapeutic resistance can arise from muta-

tions in ESR1, which can drive estrogen-independent transcription and

proliferation. e highly potent, non-steroidal oral selective ER degrader

giredestrant achieves robust ER occupancy and is active regardless

of ESR1 mutation status. Phase I data indicate that giredestrant is well

tolerated, with encouraging activity as a single agent and in combination

with the CDK4/6 inhibitor palbociclib.

Methods: persevERA BC (NCT04546009) is a double-blind, placebo-

controlled, randomized, multicenter phase III study designed to evaluate

the ecacy and safety of 1L giredestrant + palbociclib in pts with ER+/

HER2– LA/mBC. Randomization: 1:1 to either giredestrant (30 mg PO)

plus letrozole placebo QD or letrozole (2.5 mg PO) plus giredestrant pla-

cebo QD on Days 1–28 of each 28-day cycle, with palbociclib (125 mg PO

QD) on Days 1–21 of each 28-day cycle. Men and premenopausal women

will receive an LHRH agonist. Eligibility: females or males ≥18 years old

with measurable disease or evaluable bone disease and no prior treat-

ment for advanced disease. Pts who received prior fulvestrant, who have

relapsed within 12 months of completion of (neo)adjuvant therapy with

an AI and/or prior therapy with CDK4/6 inhibitor are not eligible; relapse

during tamoxifen therapy but >24 months aer the start of tamoxifen

therapy is allowed. Stratication: site of disease, disease-free interval since

the end of (neo)adjuvant therapy, menopausal status, geographic region.

progression-free survival. Secondary endpoints include overall survival,

objective response rate, duration of response, clinical benet rate, QoL

and safety. Enrollment is open; target recruitment is 978 pts.

Disclosure Statement: e authors declare no conict of interest.

306

Current treatment landscape of advanced triple negative

breast cancer patients among a network of oce-based

oncologists and gynecologists in Germany

Michael Braun1,2; Oliver J. Stoetzer3; Christoph Salat3; Jens Borchardt4;

Ralf Reichelt4; Andra Kuske5

1Brustzentrum Rotkreuzklinikum München, München, Deutschland

2MVZ für Senologie, Gyn. Onkologie und Spezielle Operative Gynäkologie,

München, Deutschland

3Medizinisches Zentrum für Hämatologie und Onkologie München, München,

Deutschland

4Onkotrakt AG, Hamburg, Deutschland

5Gilead Sciences GmbH, Martinsried, Deutschland

Background: Despite new developments in treatment landscape of

advanced triple negative breast cancer (mTNBC) prognosis remains poor.

Real world data on patients (pts) outside of clinical trials are rare but very

helpful to understand and improve the standard of care.

Methods: Data was collected from 48 oce-based oncologists and gyne-

cologists in Germany (DE) using oncotrace soware. Jan 2014 - Jun 2021,

7533 breast cancer (BC) pts were documented within the Onkotrakt net-

work. For descriptive statistical evaluation SPSS soware was used.

Result: BC subtypes in palliative (m) setting are distributed as follows:

1619 (64%) HER2-/HR+, 195 (8%) HER2+/HR-, 377 (15%) HER2+/HR+,

360 (14%) TNBC. Top 5 therapy regimen in 1 line (L) m setting for TNBC

(n=248): 33% taxane (+bevacizumab (bev) 48%), 21% carboplatin + che-

motherapy (carbo + CTx) (+ bev 20%), 13% capecitabine (cap) (+ bev

75%), 8% atezolizumab + nab-Paclitaxel (atezo + nab-P), 5% vinorelbin

(vino). Top 5 therapies in ≥2L (n=372): 17% eribulin, 16% carbo + CTx (+

beva 10%), 12% taxane (+ beva 34%), 12% anthracycline (+ beva 6%), 11%

vino. Median duration of 1L top 5 therapies was 91 d taxane, 112 d carbo +

CTx, 140 d cap, 154 d atezo + nab-P and 85 d vino. Median duration of 2L

top 5 therapies was 126 d taxane, 88 d carbo+CTx 76 d cap, 113 d eribulin,

77 d vino. In ≥3L duration of treatment decreased.

Discussion: Combination of taxane, cap or platinum with beva for

mTNBC is very common in DE. Atezo + nab-P approved in 2019 gained

importance in 1L m setting while eribulin is the most common therapy in

≥2L. Duration of 1L and ≥2L therapy conrmed the diculty in treating

mTNBC pts.

Conclusion: Here, we describe the treatment reality for mTNBC pts in a

network of oce-based oncologists and gynecologists in DE. Pts receive

various CTx options but only a few targeted therapies. Since 2019 PD-L1

inhibitors (i) for PD-L1-positive tumors as well as PARPi for pts with

BRCA germline mutations become more important. Recent study data on

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 25

antibody-drug-conjugates e.g. Sacituzumab Govitecan may provide novel

treatment options for mTNBC pts.

Disclosure Statement: e authors declare the following: Funding: Gilead

Sciences GmbH

309

Impact of Tucatinib on Progression Free Survival in Patients

with HER2 + Metastatic Breast Cancer and Brain Metastases

Sibylle Loibl1; Nancy Lin2; Rashmi K. Murthy3; Sara A. Hurvitz4;

Virginia Borges5; Mafalda Oliveria6; Catherine Oakman7; Sarah Khan8;

Cynthia Lynch9; Kelly Westbrook10; Catherine Doyle11; Mattea Reinisch12;

Marco Callenoni13; Dennis Slamon4; Gabriel Hortobagyi3; Eric Winer2;

Jorge Ramos14; Wentao Feng15; Thomas Bachelot16

1GBG Forschungs GmbH, Neu-Isenburg, Deutschland

2Dana Farber Cancer Institute, Boston, USA

3MD Anderson Cancer Center, University of Texas, Houston, USA

4UCLA Medical Center, Jonsson Comprehensive Cancer Center, Los Angeles, USA

5University of Colorado Cancer Center, Aurora, USA

6Hospital Universitario Vall D’Hebron, Barcelona, Spanien

7Sunshine Hospital, St. Albans, Australien

8Nottingham University Hospitals NHS Trust, Department of Oncology,

Nottingham, Vereinigtes Königreich

9Cancer Treatment Centers of America, Western Regional Medical Center,

Goodyear, USA

10Duke University Medical Center, Durham, USA

11Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval, Quebec, Kanada

12Kliniken Essen-Mitte - Evang. Huyssens-Stiftung, Essen, Deutschland

13Istituto Europeo di Oncologia, Milano, Italien

14Seagen Inc., Clinical Development, Bothell, USA

15Seagen Inc., Biostatistics, Bothell, USA

16Centre Léon Bérard, Lyon, Frankreich

Tucatinib (TUC) is an oral tyrosine kinase inhibitor highly specic for

HER2. TUC is approved in multiple regions for use in combination with

trastuzumab (T) and capecitabine (C) in adult patients (pts) with advanced

unresectable or metastatic HER2+ breast cancer, including pts with brain

metastases (BM), who have received 2 prior anti-HER2–based regimens.

In the pivotal HER2CLIMB trial, TUC added to T and C resulted in sta-

tistically signicant improvements in PFS and OS in HER2+ metastatic

breast cancer pts with and without BM (Murthy, NEJM 2020). We present

exploratory analyses of PFS by type of BM in HER2CLIMB.

HER2CLIMB (NCT02614794) pts were randomized 2:1 to receive

TUC or placebo combined with T and C. All pts had baseline brain MRI.

BM were classied as untreated, treated stable, or treated and progressing.

PFS per investigator and OS were analyzed by treatment arm in stable BM

pts (treated stable) and active BM pts (untreated + treated progressing),

using standard RECIST 1.1 assessing disease in both body and brain.

At baseline, 291 pts (48%) had BM: 198 (48%) in the TUC arm and 93

(46%) in the control arm. In pts with stable BM (n=117), median (95%

CI) PFS was 7.5 mo (5.4, 9.6) in the TUC arm vs 5.0 mo (2.0, 5.6) in the

placebo arm (HR: 0.56; 95% CI: 0.33, 0.96; P=0.03). In pts with active BM

(n=174), median PFS was 7.6 mo (5.7, 8.5) in the TUC arm vs 4.1 mo (3.1,

4.3) in the placebo arm (HR: 0.38; 95% CI: 025, 0.58; P<0.00001). In pts

with treated progressing BM (n=108), median PFS was 7.6 mo (5.7, 9.6) in

the TUC arm vs 4.1 mo (3.1, 4.3) in the placebo arm (HR: 0.36; 95% CI:

0.21, 0.63; P=0.0002). In pts with untreated BM (n=66), median PFS was

6.9 mo (5.5, 9.6) in the TUC arm vs 3.6 mo (1.5, 7.5) in the placebo arm

(HR: 0.47; 95% CI: 0.24, 0.92; P=0.02).

Addition of TUC to T and C signicantly improved PFS regardless of

BM type, indicating delay of progression not only in the body but also in

the brain. Patients with active BM (typically excluded from HER2+ MBC

trials) had substantially longer PFS with TUC treatment.

Reference:

1 Murthy et al. N Engl J Med. 2020;382:597–609.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

340

Toxicity of chemo- versus endocrine therapy in combination

with dual HER2-targeted therapy with trastuzumab and

pertuzumab plus ribociclib in patients with HER2 positive

and hormone-receptor positive metastatic breast

cancer - results from an Interim Safety Analysis of DETECT V

Fabienne Schochter1; Jens Huober1,2; Tanja Fehm3; Volkmar Müller4;

Brigitte Rack1; Marianne Just5; Jacqueline Sagasser6; Marcus Schmidt7;

Thomas Decker8; Andreas Hartkopf9; Andreas Schneeweiss10;

Thomas W. P. Friedl1; Wolfgang Janni1

1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm,

Deutschland

2Brustzentrum, Kantonsspital St.Gallen, St. Gallen, Schweiz

3Klinik für Frauenheilkunde und Geburtshilfe, Heinrich-Heine-Universität

Düsseldorf, Düsseldorf, Deutschland

4Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-

Eppendorf, Martinistraße 52, Hamburg, Deutschland

5Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Deutschland

6Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Augsburg,

Augsburg, Deutschland

7Klinik für Frauenheilkunde und Geburtshilfe, Universitätsmedizin der Johannes

Gutenberg-Universität Mainz, Mainz, Deutschland

8Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,

Deutschland

9Department für Frauengesundheit, Universitätsklinikum Tübingen, Tübingen,

Deutschland

10Nationalen Centrum für Tumorerkrankungen (NCT), Universitätsklinikum

Heidelberg, Heidelberg, Deutschland

Background: Metastatic breast cancer (MBC) is a non-curable disease

and preserving quality of life is important for the patients. An emerging

body of evidence supports treatment options without chemotherapy in

HER2 positive and hormone-receptor positive metastatic breast cancer.

Methods: DETECT V / CHEVENDO is a prospective randomized phase

IIIa clinical trial to assess safety and ecacy of a dual human epidermal

growth factor receptor 2 protein (HER2)-targeted therapy with trastu-

zumab and pertuzumab combined with either chemotherapy (arm A) or

endocrine therapy (arm B) in patients with HER2- and hormone receptor

(HR)-positive MBC. With amendment no 1, the CDK4/6 inhibitor ribo-

ciclib was added as study treatment in both arms. is report analyses

the tolerability and safety of the study treatment for the rst 15 patients

randomized to both arms aer the addition of ribociclib.

Result: Overall, 232 adverse events (AEs) were reported, with 154 (66.4%)

AEs for patients in the chemotherapy arm and 79 (33.6%) AEs for patients

in the endocrine therapy arm. ere were 33 grade 3 AEs (21 in the che-

motherapy arm and 12 in the endocrine therapy arm) and 3 grade 4 AEs

(ileus, increased alanine aminotransferase, neutropenia) in the chemo-

therapy arm. Of the 9 serious adverse events (SAEs) observed, one was

death due to disease progression and 8 cases were classied as SAEs

because they required hospitalization. Only one of the observed SAEs was

regarded as a serious adverse reaction (SAR) – one patient in the endo-

crine arm developed chills suspected to be caused by trastuzumab.

Discussion: e observed AEs were within the expected range, with

diarrhea and neutropenia being the most frequent. Overall, this interim

analysis showed less toxicity in the endocrine therapy arm than in the

chemotherapy arm.

Conclusion: e combination of a dual HER2-targeted therapy with

endocrine treatment and ribociclib shows good tolerability and may be

a preferred treatment option for patients with HER2- and HR-positive

MBC, if further analyses of ecacy and quality of life support a favorable

risk-benet-ratio.

Disclosure Statement: e authors declare the following: Speaker fees/ honoraria:

Roche, Pzer, Novartis, Lilly, AstraZenica Consultat; none Research grants:

AstraZenica

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts26

353

Glutaminase inhibition as a therapeutic option for tamoxifen-

resistant breast cancer

Gerd Bauerschmitz; Friederike Steifensand; Julia Gallwas;

Carsten Gründker

Universitätsmedizin Göttingen UMG, Frauenklinik, Göttingen, Deutschland

Purpose: In the therapy of estrogen receptor α (ERα)-positive breast

cancer (BC), the focus is on hormone sensitivity targeting therapy with

selective estrogen receptor modulators (SERMs) such as 4-hydroxytamox-

ifen (4-OHT). However, this therapy is oen limited by development of

resistance. e upregulated glutaminolysis in BC cells could be used as

an additional therapeutic target. In this study, we have analyzed the use

of glutaminase inhibitor CB-839 to target the increased glutaminolysis.

Methods: Sublines of ERα-positive MCF7 and T47D BC cells were estab-

lished, which were developed to be resistant to 4-OHT. Cell viability was

analyzed using Alamar Blue. Induction of apoptosis was assessed by mea-

suring the mitochondrial membrane potential. Expression of c-Myc was

quantied by Western blot. Transient c-Myc gene silencing was conducted

using RNA interference.

Results: Co-treatment using 4-OHT and CB-839 showed signicantly

stronger inhibitory eects on viability compared to treatment with 4-OHT

or CB-839 only. Tamoxifen-resistant BC cells, compared to non-resistant

cells exhibited a reduced cell viability under CB-839 treatment. Further,

tamoxifen-resistant BC cells showed increased expression of proto-onco-

gene c-Myc which could be reduced by CB-839 treatment. Suppression of

c-Myc expression using specic siRNA completely abolished resistance to

4OH-tamoxifen.

Discussion: Our data suggest that combined treatments aecting metab-

olism of BC are suitable depending on cellularity and resistance status.

In addition, the anti-metabolic treatments aected expression of c-Myc,

a key player in the regulation of cancer cell metabolism and resistane

against 4-OHT.

Conclusion: Anti-metabolic treatment reduces c-Myc expression leading

to loss of tamoxifen-resistance. is fact should receive clinical attention

in the future.

Disclosure Statement: e authors declare no conict of interest.

354

Intrinsic Breast Cancer Subtypes depending on Participation

in Mammography Screening Program

Britta Mathys1; Iris Urbschat2; Joachim Kieschke2; Gerold Hecht1

1Referenzzentrum Mammographie Nord, Oldenburg, Deutschland

2Epidemiologisches Krebsregister Niedersachsen (EKN), Registerstelle,

Oldenburg, Deutschland

Background: Breast cancer in screening participants has shown favor-

able tumor characteristics and prognostic parameters compared to symp-

tom-detected breast cancer, even including interval cancers. Our aim

was to examine the distribution of the molecular breast cancer subtypes

considering the proliferation marker Ki-67 in participants and non-

participants of the German Mammography Screening Program (MSP) in

a population-based setting.

Methods: Data from the Epidemiological Cancer Registry of Lower

Saxony with diagnosis in year 2014 were analyzed. 953 cases of invasive

breast cancer among MSP participants and non-participants (aged 50-69

years, residing in two MSP-regions of Lower Saxony with 285.634 bien-

nially entitled women) were included. e group of the MSP participants

contained cancers that were detected by screening or in the interval of 24

month aer a negative screening. e group of non-participants included

all other cancers. A modied molecular subtyping of all tumors was per-

formed according to the S3-guidelines (categories for Ki-67: ≤ 10% = low,

11-24% = intermediate, ≥ 25% = high).

Result: Breast cancers of MSP participants were more oen HER2 neg-

ative (p = 0,03) and showed lower Ki-67 percentage scores (p = 0,0003)

compared to non-participants. According to this results and aer

exclusion of missing data (17%) the distribution of the intrinsic subtypes

was as follows: Luminal A (MSP participants 38,4% vs. non-participants

26,7%), Luminal A or B (26,7% vs. 22,1%), Luminal B (21,1% vs. 30,6%),

HER2 enriched (5,1% vs. 7,8%), triple-negative (8,8% vs. 12,8%). In both

groups the distribution of Ki-67 was associated with the analyzed prog-

nostic parameters with strongest association between Ki-67 and grading

(p < 0,0001).

Discussion: According to the S3-Guidelines an adjuvant chemother-

apy can be avoided due to a more favorable prognosis in the majority

of Luminal A type breast cancers. Assuming that both groups received

a guideline-based therapy, MSP participants could be treated with less

aggressive systemic therapy compared with cancers in non-participants.

Disclosure Statement: e authors declare the following: Dr. Hecht ist Leiter

des Referenzzentrums Mammographie Nord und Leiter der Screeningeinheit

Niedersachsen Nordwest, Dr. Mathys ist als Honorarkra im Referenzzentrum

Mammographie Nord tätig und arbeitet als Befunderin. Frau Urbschat und Herr

Kieschke haben keine wirtschalichen oder persönlichen Verbindungen im unten

genannten Sinne.

361

Association of polygenic risk scores with extreme ages at

onset of primary breast cancer in BRCA1/2 mutation carriers

Corinna Ernst1; Julika Borde1; Yael Laitman2; Barbara Wappenschmidt1;

Christoph Engel3; Rita Katharina Schmutzler1; Eitan Friedman2;

Eric Hahnen1

1Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology

(CIO), University Hospital Cologne, Cologne, Deutschland

2Oncogenetics Unit, Sheba Medical Center, Tel Aviv, Israel

3Institute for Medical Informatics, Statistics and Epidemiology, University of

Leipzig, Leipzig, Deutschland

Purpose: Clinical management of BRCA1/2 mutation carriers demands

for accurate age-dependent estimates of breast cancer (BC) risks.

erefore, the utility of polygenic risk scores (PRSs) for the discrimination

of extreme phenotypes with respect to age at onset, i.e., early diagnosis

(ED) before the age of 35 years and BC-free survival until the age of 60

years (late/no diagnosis, LD) in BRCA1/2 mutation carriers was assessed.

Methods: e overall BC PRS, estrogen receptor (ER)-positive BC PRS,

and ER-negative BC PRS as developed by Kuchenbaecker et al. [1] for BC

risk discrimination in female BRCA1/2 mutation carriers were employed

for PRS computation in a curated sample of 295 women of European

descent carrying pathogenic (class 4/5) variants in the BRCA1 (n=183)

or the BRCA2 gene (n=112), and were either diagnosed with primary BC

before the age of 35 years (ED, n=162, mean age at diagnosis: 28.3 years,

range: 20 to 34 years) or not aected by BC until the age of 60 years (LD,

n=133). Binomial logistic regression was applied to assess the association

of standardized PRSs with either ED or LD. Analyses were adjusted by BC

family history and localisation of pathogenic gBRCA1/2 variants in the

corresponding breast or ovarian cancer cluster regions.

Results: For BRCA1 mutation carriers, the standardized overall BC PRS

displayed the strongest association with ED (odds ratio (OR) = 1.62; 95%

condence interval (CI): 1.16–2.31, p = 0.007). For BRCA2 mutation car-

riers, the standardized PRS for ER-negative BC displayed the strongest

association with ED (OR = 2.27, 95% CI: 1.45–3.78, p < 0.001).

Discussion: Our results demonstrate the contribution of PRSs to the

development of extreme phenotypes of BRCA1/2 mutation carriers with

respect to age at primary BC diagnosis.

Conclusions: PRSs are essential prequisites for personalized BC risk pre-

diction in clinical management of healthy women with BRCA1/2 germline

mutations.

Reference:

[1] Kuchenbaecker, K. et al. Evaluation of polygenic risk scores for breast and

ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers. J Natl

Cancer Inst, 2017.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 27

426

The BEGYN study: Assessment of quantity and quality of

physical activity, tness, body composition, immunological

biomarkers, and psychological parameters during the rst

year after diagnosis of breast cancer

Cosima Zemlin1; Caroline Stuhlert1; Julia Theresa Schleicher1;

Carolin Wörmann1; Laura Altmayer1; Marina Lang1;

Laura-Sophie Scherer1; Ida Thul1; Carolin Müller1; Elisabeth Kaiser2;

Regine Stutz2; Sybelle Goedicke-Fritz2; Laura Ketter3; Gudrun Wagenpfeil4;

Michael Zemlin2; Georges Stegen3; Erich-Franz Solomayer1

1Saarland University Medical Center, Department for Gynecology, Obstetrics

and Reproductive Medicine, Homburg, Deutschland

2Saarland University Medical Center, Department for General Pediatrics and

Neonatology, Homburg, Deutschland

3University of Luxembourg, Department of Behavioural and Cognitive Sciences,

Institute for Health and Behaviour, Esch-sur-Alzette, Luxemburg

4Saarland University Campus Homburg, Institute for Medical Biometry,

Epidemiology and Medical Informatics (IMBEI), Homburg, Deutschland

Purpose: e BEGYN study prospectively examines the relationship

between physical activity and course of disease and therapy (e.g. dose

adjustments), laboratory parameters, tness, body composition and men-

tal health.

Methods: Non-metastatic breast cancer patients were recruited at the

breast center of the Saarland University Hospital. Before starting ther-

apy and aer 3, 6, 9 and 12 months, all patients are assessed by tread-

mill spiroergometry, routine laboratory, ow cytometry of leukocyte

subpopulations, cytokine proles in plasma (MagPix), body composition

(bioimpedance) and psychometry using standardized questionnaires on

quality of life, stress, mental health, depression, etc. (EORTC-QLQ (BR23,

C30), HADS, Distress ermometer, MDBF, SPG). Each patient wears a

tness tracker (Fitbit Charge 3™). Metabolic equivalents (METs) are calcu-

lated based on a daily exercise diary. Membership fees in sports clubs are

reimbursed. Registration number: DRKS00024829.

Results: Between 10/2019 and 01/2021 197 of 387 newly aected patients

met the inclusion criteria and 110 patients agreed to participate in the

BEGYN study. Age 54.1 +/- 11.8 years (mean, SD). 66 patients received

chemotherapy and 41 endocrine therapy exclusively. In 22 of 42 (52%)

patients that completed the one year follow up until Aug 2021, tness

(resting heart rate) was better at the end of the study than at the begin-

ning, in 16 (38%) it was worse. In contrast, the muscle mass decreased in

64 % of the patients and increased in 29%.

Discussion: e recruitment goal (n = 110) of the BEGYN study was

achieved. Initial results indicate that tness can increase even under onco-

logical therapy, whereas muscle mass decreased in the majority, even with

better tness during the year aer the diagnosis of breast cancer.

Conclusion: e BEGYN study will improve the understanding of the

relationship between physical activity and somatic and psychological vari-

ables in breast cancer and provide data to develop individualized training

recommendations for our patients.

Disclosure Statement: e authors declare no conict of interest.

429

A new approach (Hilotherapy®) to prevent chemotherapy –

induced Polyneuropathy (CIPN) - UPDATE

Trudi Schaper1; Maren Darsow1; Mahdi Rezai2; Petra Hegener3;

Günther Schmutz3

1Luisenkrankenhaus GmbH & Co KG, Düsseldorf, Deutschland

2European Breast Center Dr. Rezai, Düsseldorf, Deutschland

3MVZ Düsseldorf, Düsseldorf, Deutschland

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is

an adverse eect of many commonly used chemotherapeutic agents, espe-

cially taxane-based regimen (Paclitaxel, nab-Paclitaxel, Docetaxel). CIPN

reduces patients health-related quality of life for years and oen results in

dose delay, dose reduction or treatment discontinuation. e preventive

use of controlled thermotherapy (Hilotherapy®) prevents CIPN.

Method:189 breast cancer patients used a new thermotherapy, a device

equiped with hand /foot cus to allow a constant cooling.

Continous cooling of extremities was performed 30 minutes before to

60minutes aer completing drug infusion with a temperature of 10-12°C.

CIPN symptoms were evaluated aer each cytotoxic cycle using common

terminology criteria for adverse events (CTCAE).

Sustainability of results was assessed by long-term datas (every 3 months).

151 patients used the prophylactic Hilotherapy® for each cytotoxic treat-

ment (Group 1: primary Prophylactic Hilotherapy® - pPHT).

38 patients used reactive secondary Hilotherapy® (Group 2: rSHT). Hands

and feet were cooled aer onset of symptoms of CIPN (grade 1-3).

Results:

Group pPHT: Out of 151 patients who used pPHT, 141 patients (93%)

developed none or mild symptoms of CIPN (grade 0-1). 9 patients (6 %)

reported grade 2, 1 patient grade 3 (0,8%) toxicity. 4 weeks aer last che-

motherapy, no patient suered grade 3 CIPN; grade 2 toxicities have been

reduced to 7 patients (6% to 4,7%). 69% described no symptoms (grade

0), 26,4% mild symptoms of CIPN (grade 1). 4 – 10 months aer chemo-

therapy 98% of patients have no CIPN>grade 1.

Group rSHT: Without using pPHT 90% of the patients developed CIPN

symptoms. 50% suered grade 3 2 CIPN. Using rSHT for all remaining

chemotherapies, progression of CIPN was stopped, reduction of toxici-

ties was seen. At last chemotherapy treatment grade 2 & 3 toxicities were

reduced from 50% to 25%.

Conclusions: Preventive Hilotherapy® prevents CIPN > grade 1 in 93% of

patients. No dose reductions or treatment discontinuation was necessary,

and quality of life is maintained.

Disclosure Statement: e authors declare no conict of interest.

436

Abemaciclib combined with adjuvant endocrine therapy

in patients with high risk early breast cancerwho received

neoadjuvant chemotherapy (NAC)

Tjoung-Won Park-Simon1; Miguel Martin2; Roberto Hegg3; Sung-Bae Kim4;

Michael Schenker5; Daniela Grecea6; Jose Angel Garcia-Saenz7;

Konstantinos Papazisis8; Quchang Ouyang9; Aleksandra Lacko10;

Berna Oksuzoglu11; James Reeves12; Meena Okera13; Laura Testa14;

Chikako Shimizu15; Ran Wei16; Tammy Forrester16; Maria Munoz16;

Annamaria Zimmermann16; Desiree Headley16; Stephen Johnston17

1Medizinische Hochschule Hannover, Hannover, Deutschland

2Hospital General Universitario Gregorio Marañon, Madrid, Spanien

3Clin. Pesq.e Centro, São Paulo, Brasilien

4Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republik

Korea

5Centrul de Oncologie Sf. Nectarie SRL, Craiova, Rumänien

6Institutul Oncologic “Prof.Dr. Ion Chiricuta” Cluj-Napoca, Cluj-Napoca,

Rumänien

7Hospital Clinico San Carlos, Madrid, Spanien

8Euromedica - General Clinic of Thessaloniki, Thessaloniki, Griechenland

9Hunan Cancer Hospital, Changsha, China, VR

10Dolnoslaskie Centrum Onkologii, Wroclawski Uniwersytet Medyczny,

Breslau,Polen

11Dr.Abdurrahman Yurtaslan Ankara Oncology Training & Res Hosp,

Ankara,Türkei

12Florida Cancer Specialists/Sarah Cannon Research Institute SCRI,

FortMyers,USA

13Adelaide Cancer Centre, Kurralta Park, Australien

14Instituto D’Or de Pesquisa e Ensino (IDOR), São Paulo, Brasilien

15Präfektur Tokio, National Center for Global Health and Medicine, Tokio, Japan

16Indianapolis, Eli Lilly and Company, Indianapolis, USA

17Royal Marsden NHS Foundation Trust, London, Vereinigtes Königreich

Background: monarchE (phase 3, open-label, randomized study evalu-

ating abemaciclib combined with adjuvant endocrine therapy [ET] com-

pared to ET alone in patients [pt] with HR+, HER2-, high risk early breast

cancer [EBC]) resulted in a statistically signicant improvement in inva-

sive disease-free survival (IDFS; HR=.713; 95%CI=.583, .871).

Methods: Pt with ≥4 positive nodes (LNS)/1-3 LNS and either Grade

3 disease, tumor size ≥5 cm or central Ki-67 ≥20% were eligible. Prior

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts28

chemotherapy (NAC, adjuvant, none) was a stratication factor. We

present results of the prespecied subgroup of pt who received NAC.

Results and Discussion: Of 5637 randomized pt, 2056 received NAC.

Chosen regimen included anthracycline +cyclophosphamide +taxane

for 84.8% and anthracycline+taxane for 4.4%. In pts who received NAC,

29.1% had tumors ≥5 cm at diagnosis, 36.7% had tumors with histologic

grade 3 and 55.2% had LNS ≥4+. Central Ki-67 prior to NAC was ≥20%

in 64.8% pt with available Ki-67 results (664 (32.3%) pt had missing Ki-67

results). A multivariate cox regression analysis of IDFS in intent-to-treat

(ITT) population identied prior chemotherapy as prognostic, suggesting

pt who received NAC were at risk of a worse outcome. For pt who received

NAC, abemaciclib+ET demonstrated treatment benet in terms of IDFS

vs ET alone (IDFS events: abemaciclib+ET=92; ET alone=148; HR=.614,

95%CI=.473, .797) with 2-year IDFS rates of 87.2% (95%CI=84.1, 89.8) vs

80.6% (77.0, 83.6). ere was also a benet in distant relapse-free survival

(DRFS) (DRFS events: abemaciclib+ET=77; ET alone=125; HR=.609,

95%CI=.459, .809), with 2-year DRFS rates of 89.5% (95%CI=86.7, 91.8)

vs 82.8% (79.3, 85.8).

Conclusions: Patients with HR+, HER2- EBC who received NAC were

at a higher risk of recurrence. In this subgroup, abemaciclib+ET demon-

strated a clinically meaningful treatment benet in IDFS and DRFS,

which was numerically greater than in the ITT population. Safety data

were consistent with abemaciclib safety prole.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

441

Comparison of clinical, histopathological, therapeutic

factorsand survival between 2510 male and 307634 female

patients with invasive breast cancer – results from a large

population-based cohort study in Germany

Marion Graf1; Michael Gerken1,2; Monika Klinkhammer-Schalke1,2;

Simone Schrodi3; Jutta Engel3; Armin Pauer1,2; Olaf Ortmann4;

Elisabeth C. Inwald4

1Tumour Center, Institute for Quality Management and Health Services

Research, University of Regensburg, Regensburg, Deutschland

2Bavarian Cancer Registry - Regional Centre Regensburg, Bavarian Health and

Food Safety Authority (LGL), Regensburg, Deutschland

3Munich Cancer Registry (MCR) at the Institute of Medical Information

Processing, Biometry, and Epidemiology, Ludwig-Maximilians-University,

Bavarian Cancer Registry - Regional Centre Munich, Bavarian Health and Food

Safety Authority, München, Deutschland

4University Medical Center Regensburg, Department of Gynecology and

Obstetrics, Regensburg, Deutschland

Purpose: To date few data on breast cancer in men are available. erapy

recommendations are mainly based on those for postmenopausal women.

Evidence suggests higher mortality in male breast cancer. e present

study compared clinical, histopathological and therapeutic factors as well

as survival rates between men and women with malignant neoplasms of

the breast.

Methods: In the present cohort study data from 18 German clinical

cancer registries were analyzed retrospectively. 2,510 male and 307,634

female patients with malignant neoplasms of the breast were included.

Results: Men showed signicantly worse prognostic factors at date of diag-

nosis, e.g. higher stage and positive lymphatic invasion. With a median

follow-up time of 8.8 years, 5-year overall survival rate in women was

80.4% vs. 69.6% in men. Hazard ratio derived from univariable Cox

regression was 1.759 (95 % CI: 1.652 - 1.873; p <0.001). In multivariable

Cox regression with adjustment for age at diagnosis, tumor side, histology,

stage, grading, lymphatic and venous invasion, hormone receptor status,

HER2/neu, Ki-67, and year of diagnosis the mortality risk for men was

still 1.322 times higher than for women (95 % CI: 1.241 - 1.407; p <0.001).

Also recurrence-free survival was worse in men. Comparing systemic

therapies in corresponding indication groups, treatment rates were 9.5%

to 23.8% lower in men than in women. e inclusion of systemic thera-

pies in the multivariable analysis did not change the dierence of mortal-

ity risk between men and women. However, when guideline-concordant

therapy was performed in men a similar treatment benet as in women

was observed.

Discussion: Even taking account dierences in patient and tumor charac-

teristics and treatment rates mortality risk remains higher in men. Other

inuences such as lifestyle or biological factors could play a role.

Conclusions: To explain the disparity between male and female breast

cancer survival and to nd possible improvements for male patients,

future projects should include lifestyle and biological factors.

Disclosure Statement: e authors declare no conict of interest.

479

Intraoperative circular resection of the breast in patients

withprimary breast cancer in stage 0 to III - experience

of a singular breast center

Wladimir Pauker

Rotenburg (Wümme), AGAPLESION DIAKONIEKLINIKUM ROTENBURG

gemeinnützige GmbH, Frauenklinik, Rotenburg (Wümme), Deutschland

Background: e circular resection of the adjacent breast tissue aer

tumor resection signicantly reduces the number of tumor-involved mar-

gins and thus both the number of repeated breast-conserving operations

and the number of mastectomies in patients with primary breast cancer

in stage 0-III.

Methods: From December 17, 2019 to July 9, 2021, 273 patients with pri-

mary breast cancer in stages 0 to III underwent breast-conserving sur-

gery. 176 (64.5%) (group I) patients were operated on with a degree of

complexity I to II according to Wallwiener D. et al.1, Breast-conserving

surgery (BEO). In the other 97 (35.5%) (Group II) patients, oncoplastic

techniques with degrees of complexity III to V were used. All patients

received either specimen radiographs or sonographies intraoperatively to

reduce the likelihood of postoperative resections. 43 (44.3%) of 97 breast

cancer patients received a circular resection of the breast tissue adjacent

to the tumor in addition to advanced oncoplastic techniques and indepen-

dent of intraoperative controls of marginal distances.

Result: e number of patients in group I who required repeated

breast-conserving surgery or mastectomy was 39 / 22.1% of 176. In group

II patients with complex oncoplastic techniques with and without intra-

operative resections, the number of repeated resections was equal to

Operations 8 / 14.8% of 54 and 4 / 9.3% of 43, respectively.

Conclusion: We were able to determine that the use of complex onco-

plastic breast-conserving operations leads to a reduction in the number of

repeated interventions from 22.1% to 14.8% and the additional intraoper-

ative resection reduces the number of repeat operations by more than half

from 22.1% to 9.3%.

Reference:

1. Wallwiener, D.; Hahn, M.; Marx, M.; P. Renner, S.; Y. Brucker, S.; Homann,

J:Plastische Chirurgie. Die Bedeutung der Onkoplastik in der modernen

Senologie. Geburtshilfe und Frauenheilkunde2015; 75(10): 977–990

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 29

504

Safety interim analysis (SIA) of the phase III postneoadjuvant

SASCIA study evaluating sacituzumab govitecan (SG) in

patients (pts) with primary HER2-negative breast cancer (BC)

at high relapse risk after neoadjuvant chemotherapy (NACT)

Frederik Marmé1; Claus Hanusch2; Jenny Furlanetto3; Patrick Morris4;

Theresa Link5; Carsten Denkert6; Peter Andreas Fasching7;

Christian Jackisch8; Silvia Antolín9; Christine Solbach10; Philippe Aftimos11;

Jens Huober12; Michael Untch13; Marija Balic14; Mattea Reinisch15;

Jens-Uwe Blohmer16; Anthony Concalves17; Julia Rey3; Thomas Büchele3;

Sibylle Loibl3

1Medical Faculty Mannheim, Heidelberg University, University Hospital

Mannheim, Mannheim, Deutschland

2Rotkreuzklinikum München, München, Deutschland

3German Breast Group, Neu-Isenburg, Deutschland

4Beaumont Hospital, Dublin, Irland

5Department of Gynecology and Obstetrics, Technische Universität Dresden,

Dresden, Deutschland

6Institute of Pathology, Philipps University Marburg and Marburg University

Hospital (UKGM), Marburg, Deutschland

7Universitätsklinikum Erlangen, Erlangen, Deutschland

8Sana Klinikum Oenbach GmbH, Oenbach am Main, Deutschland

9Complejo Hospitalario Universitario A Coruña-Hospital Teresa Herrera (CHUAC),

Servicio de Oncología Médica (planta baja), Coruña, Spanien

10Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland

11Clinical Trials Conduct Unit, Institut Jules Bordet - Université Libre de Bruxelles,

Brüssel, Belgien

12Kantonsspital St.Gallen, Brustzentrum, Departement Interdisziplinäre

medizinische Dienste, St. Gallen, Schweiz

13Helios Klinikum Berlin-Buch, Berlin, Deutschland

14Medical University of Graz, Clinical Department of Oncology, Graz, Österreich

15Kliniken Essen-Mitte, Essen, Deutschland

16Gynäkologie mit Brustzentrum, Charité-Univesitätsmedizin Berlin

17Institute Paoli-Calmettes, Marseille, Frankreich

Background: SASCIA (NCT04595565) is an ongoing phase III study ran-

domising pts with HER2- BC and residual disease aer NACT or hor-

mone receptor (HR)+ with a CPS+EG score ≥3 or 2 and ypN+ aer NACT

to SG or treatment of physician´s choice (TPC, capecitabine, platinum,

observation). We present the results of the pre-planned SIA.

Methods: e analysis was performed aer the rst 50 randomized pts

had completed 4 therapy cycles. Pts were included if they received ≥2

cycles, were observed ≥6 wks or discontinued earlier. Adverse events

(AEs) grade (G) 1-4, G3-4 and compliance (reductions, delays, discontin-

uation) between arms were assessed.

Result: At the time of the analysis, 142 pts were randomized, 88 were

included in the SIA. 45 pts received SG, 32 capecitabine, 11 were observed.

Median age was 46 (24-71) in SG vs 51 (32-74) yrs in TPC arm, median

BMI 25.8 (20.0-42.6) vs 23.8 (18.2-35.4) kg/m2, more pts in SG arm had

a Ki67>20% (N=29, 64.4% vs N=21, 48.8%); 30 (66.7%) vs 29 (67.4%)

were HR-, 15 (33.3%) vs 14 (32.6%) HR+. 44 (97.8%) vs 29 (72.5%) had

hematological AEs G1-4, 25 (55.6%) vs 0 G3-4; 45 (100%) vs 36 (83.7%)

had non-hematological AEs G1-4, 15 (33.3%) vs 9 (20.9%) G3-4. No death

occurred. 6 (13.6%) pts under SG vs 3 (9.4%) under capecitabine discon-

tinued therapy prematurely; 30 (66.7%) vs 13 (43.2%) had ≥1 dose delay,

due to hematological (N=21, 46.7% vs N=3, 10.0%) and non-hematologi-

cal AEs (N=3, 6.7% vs N=7, 23.3%); 12 (26.7%) vs 9 (28.1%) had ≥1 dose

reduction (hematological N=6, 13.3% vs N=1, 3.1%; non-hematological

N=5, 11.1% vs N=6, 18.8%).

Discussion: SG showed a higher rate of AEs compared to TPC, which

includes observation only. AEs, especially G3-4 AEs rate were in line with

the known safety prole of SG and led to more dose delays.

Conclusion: AEs due to SG therapy were well manageable using the rec-

ommended supportive measures. e study continues as planned.

Disclosure Statement: e authors declare that there are conicts of interest.

e connections were submitted to the congress organizer KUKM GmbH and

KUKM can disclose them if needed.

506

Remote-monitoring among patients undergoing

chemotherapy in the out-patient setting for early detection of

infections

Heike Jansen1; Anna Eichhorn1; Jannina Schaller1; Veronika Langhans1;

Kirsten Große Lackmann2; Marko Wilhelm3; Marion Kiechle1

1Klinikum rechts der Isar, TU München, Frauenklinik und Poliklinik, München,

Deutschland

2Spital Zollikerberg, Zollikerberg, Schweiz

3AIM - Apps in Medicine GmbH, München, Deutschland

Background: Due to immunosuppressive oncologic therapy patients are

at risk for infections. In case of COVID-19, patients have a high risk even

to die due to this infection, especially when they have a progressive dis-

ease. But also dose-reductions, -modications or postponing of chemo-

therapy cycles result in disease-progression and are associated with early

deaths (1,2). In this study we oer patients at risk user-friendly technolo-

gies for transmitting biosignal-data and patient reported outcome moni-

toring (PROM) data for early detection of infections.

Methods: We designed a monocenter prospective cohort study using

PROM via app and remote monitoring via photoplethysmography (PPG).

e application of these technologies enables an early detection of infec-

tions and therefore initiation of medical interventions. e study is con-

ducted as feasibility analysis; primary endpoints are adherence (according

to wearing time) and technical robustness.

Result: We expect study results in 4th quarter 2022.

Discussion: e applied user friendly technologies can be used in the

out-patient setting for transmission of biodata and symptoms; but also

for a better communication between patients and physicians. is results

in medical interventions at an early stage for treatment of infections. is

study is conducted in a cooperation with the department of cardiology,

using the infrastructure of the TUM telemedicine-center. Long-term

objective ist to establish an expandable remote-monitoring infrastructure

for the public health sector.

Conclusion: By the use of remote-monitoring and PROM, we obtain an

increase in safety for cancer patients undergoing immunosuppressive

oncologic therapy during COVID-19 pandemia.

Indication of source:

1 Warner JL, CCC19, ASCO 2020

2 Hatsy S, Inzidenz und Prädiktoren von Chemotherapie-Modikationen und

deren Einuss auf das Überleben von Patientinnen mit Ovarialkarzinom;

Dissertation TUM 2020

Disclosure Statement: M. Kiechle und K. Große Lackmann sind Anteilseigner

der AIM - Apps in Medicine GmbH. Eine Forschungsförderung erfolgt durch das

Bayerische Staatsministerium für Wissenscha und Kunst, sowie anteilig durch

das Bundesministerium für Bildung und Forschung im Rahmen der Förderung

des nationalen Pandemie Kohorten Netzwerks (NAPKON) im Netzwerk Universi-

tätsmedizin (NUM).

548

Eects of an Oncological Exercise Therapeutical Structure on

the Fatigue Syndrome of Female Breast Cancer Patients in a

Comprehensive Cancer Center

Franziska Hollnberger1; Anna Lorenz2; Monika Siegrist1;

Freerk T. Baumann2

1Fakultät für Sport- und Gesundheitswissenschaften Technische Universität

München, Lehrstuhl für Präventive und Rehabilitative Sportmedizin, München,

Deutschland

2Universität zu Köln, Klinik I für Innere Medizin Centrum für Integrierte

Onkologie Aachen Bonn Köln Düsseldorf Uniklinik Köln, Köln, Deutschland

Background: ere is growing evidence that physical activity has a pos-

itive eect in reducing side eects such as fatigue and improving Quality

of Life (QoL) in Breast Cancer patients. Recently, exercise therapy was

implemented in the S3 Guidelines for Breast Cancer patients. More stud-

ies are necessary which focus on a clinical set up, to provide evidence for

changes in treatment structures and increase the awareness in Health

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts30

insurance companies to secure nancial support. e aim of the study is

to evaluate the OTT (Oncological training and exercise therapy) program

at the University Hospital in Cologne to provide patients with access to

evidence-based exercise therapy.

Methods: Breast cancer patients which participated in the OTT program

between 2012 and 2020, were dived in two groups. e intervention group

(n = 46) trained on average between one and two days per week whereas

the control group (n = 58) trained less than once a week with a combi-

nation of strength and endurance exercise. All patients lled out various

questionnaires on physical activity, fatigue, and QoL at the anamnesis (T0)

and the end of the program (Tx).

Result: Signicant eects where only found for physical fatigue, reduced

activity and QoL among time but not between groups. However, a positive

trend towards reduced levels of fatigue and better QoL was visible in the

intervention group. A relation between the development of fatigue and

change of QoL was detected.

Discussion: e evaluation of an existing care structure brings limita-

tions such as dierent time between measurements or arbitrary allocation

to groups, which can lead to non-signicant results between groups. In

accordance with several meta-analyses, trends of this study indicate a pos-

itive eect of physical activity to reduce fatigue and improve QoL.

Conclusion: In the future, it is suggested to conduct more implementa-

tion studies in the clinical setup based on individual training. e OTT

program should be expanded to alleviate the side eects of cancer diag-

nosis and/or therapy.

Disclosure Statement: e authors declare no conict of interest.

553

Association between treatment duration and overall survival

in early-stage HER2+ breast cancer patients receiving

extended adjuvant therapy with neratinib in the ExteNET trial

Friedrich Overkamp1,2; Beverly Moy3; Bruno Coudert4; Alvin Wong5;

ArleneChan6

1onkowissen.de GmbH, Digital Health, Würzburg, Deutschland

2OncoConsult Overkamp, Berlin, Deutschland

3Massachusetts General Hospital Cancer Center, Boston, USA

4Centre Georges François Leclerc, Dijon, Frankreich

5Puma Biotechnology Inc., Los Angeles, USA

6Breast Cancer Research Centre-WA & Curtin University, Perth, Australien

Background: Completion of planned treatment has been shown to

improve clinical outcomes. In the ExteNET trial (NCT00878709), where

diarrhea prophylaxis was not mandated, 17% of patients (pts) discontin-

ued neratinib early due to diarrhea. is compares with 3.3% of pts from

the CONTROL trial (NCT02400476) who used a neratinib dose-escala-

tion strategy. Prior analyses have shown improved invasive disease-free

survival (iDFS) in pts who completed planned duration of neratinib ther-

apy in ExteNET. Here we assess outcomes, including overall survival (OS),

for pts who completed planned therapy in 3 groups from ExteNET: intent-

to-treat (ITT) population; pts with hormone receptor-positive (HR+) dis-

ease who initiated neratinib within 1y aer prior trastuzumab (HR+/≤1y,

the population neratinib is approved for in the EU); and HR+/≤1y with

residual disease post-neoadjuvant therapy (no pathologic complete

response [pCR]).

Methods: Pts with early-stage HER2+ breast cancer received oral nera-

tinib 240mg/d or placebo aer trastuzumab-based (neo)adjuvant ther-

apy. Pts who completed neratinib therapy (dened as ≥11m or cessation

of neratinib if recurrence occurred prior to 11m) were compared with

placebo (all randomized pts). iDFS and OS were analyzed using Kaplan-

Meier methods; hazard ratios (HR) with 95% condence intervals (CI)

were estimated using Cox proportional-hazards models. Data cuto: July

2019.

Result: ere were 2840 pts in the ITT population, 1334 pts in the

EU-label population (HR+/≤1y) and 295 pts with HR+/≤1y and no

pCR. In patients who completed 1 year neratinib, the 8-year OS rate was

improved by 2.0% (ITT, HR 0.78, 95%-CI 0.58-1.04), 5.8% (HR+/≤1y; HR

0.49, 95%-CI 0.29-0.78) and 13.2% (HR+/≤1y, no pCR; HR 0.29, 95%-CI

0.01-0.68), respectively, compared to placebo.

Discussion: Completion of planned neratinib was associated with

improvements in iDFS and OS in all groups evaluated.

Conclusion: ese descriptive ndings suggest that pts who receive

the recommended duration of treatment of 1y with neratinib may have

improved outcomes.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

572

Berlin Young Patients – Implementing a registry for breast

cancer in women before the age of 40

Anna Maria Hage; Mara Daniel; Friedrich Kühn; Therese Pross;

DorotheeSpeiser; Maria Margarete Karsten

Charité – Universitätsmedizin Berlin, Klinik für Gynäkologie mit Brustzentrum,

Berlin, Deutschland

Background: e risk of developing breast cancer before the age of 40

is low. However, younger age at diagnosis is oen associated with worse

prognosis. Until now, no certain phenotype correlating with younger

age could be established. Furthermore, issues such as genetic predispo-

sitions, fertility and pregnancy, therapy-associated early menopause, and

extended survivorship period require special attention in young breast

cancer patients. As current management strategies are not age-based, we

aim for a better understanding of the particularities of breast cancer in

young women.

Methods: 556 patients with breast cancer or ductal carcinoma in

situ (DCIS) diagnosed before the age of 40 and treated at Charité –

Universitätsmedizin Berlin were identied retrospectively (2008 - 2019).

Data from clinical patient records on information such as tumor stage at

diagnosis, pathologic features, genetics, therapy, recurrence, and survival

will be analyzed. A process to obtain consent to examine tumor tissues

from past surgeries is being prepared, as well as a process to include

patients prospectively.

Result: First results will be available in January 2022.

Discussion: is registry may help to identify characteristics, particular-

ities and needs of young women with breast cancer or DCIS. With this

knowledge, more specied approaches for clinical care can be explored

and potential new recommendations for age-based management strate-

gies can be considered.

Conclusion: e implementation of this registry will provide important

data about the small percentage of patients who develop breast cancer

before the age of 40. is registry will contribute to a better understanding

of the specic clinical characteristics and needs of this group of patients.

Disclosure Statement: e authors declare no conict of interest.

590

Analysis of single-cells using reverse phase protein array

(RPPA) technology

Mahdi Rivandi1; Liwen Yang1; André Franken1; Tanja Fehm1;

DieterNiederacher1; Berthold Gierke2; Michael Pawlak2; Hans Neubauer1

1Department of Obstetrics and Gynecology, Heinrich Heine University of

Duesseldorf, Duesseldorf, Deutschland

2NMI TT Pharmaservices, Protein Proling, Reutlingen, Deutschland

Background: erapy with Capivasertib, a potent pan-AKT inhibi-

tor, does not lead to response in all breast cancer patients with PIK3CA

mutated tumor cells. One reason may be that the eect of the mutation

does not translate into modulation of protein activity, making protein

analysis in single tumor cells highly interesting. is project aims to evalu-

ate protein expression and activation of dierent therapy target proteins in

the PI3K/AKT/mTOR signaling pathway at single-cell level using reverse

phase protein array (RPPA) technology.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 31

Methods: MCF-7 cells were treated with Capivasertib (5µM) to increase

phosphorylation of AKT1 protein. Single cells stained with NucBlue

(Hoechst) were micromanipulated with the CellCelectorTM device and

lysed in dierent cell lysis buers. Lysates were aspirated into a glass cap-

illary and printed in triplicates onto a Zeptosens chip. ese were blocked

and incubated with primary (p-AKT and AKT-pan) and uorescence

labelled secondary antibodies, respectively. Signals were detected by a

Zeptoreader and the treatment-to-untreated control ratios (TCR) were

calculated for pAkt and Akt total protein. Data were analyzed by Image

J soware. Western blot was conducted to conrm expression levels and

phosphorylation of Akt1.

Result: Spotting of triplicates is highly reproducible with a signal dier-

ence below 10%. e optimal amount and ratio of lysis buer is 20nL of 1:1

CLB: CSLB buer with the spotting volume of 2nL. e humidity during

spotting and the other picking/printing parameters were optimized. As

expected, TCR of pAkt/Akt is more than twofold elevated (243%) in single

treated MCF-7 cells compared to the control group in three independent

experiments. e ratios determined with single cells are in line with west-

ern blot data.

Conclusion: We have established a new and highly sensitive method to

measure expression and phosphorylation of treatment relevant proteins in

single cells to measure activation of key cancer driving signaling pathways.

Disclosure Statement: e authors declare no conict of interest

607

The Impact of Irradiation and Lipotransfer on Healthy

Mammary Cells after Breast-Conserving Surgery

Chiara-Sophia Kutz1; Tina Jost2; Luitpold Distel3;

Annika Kengelbach-Weigand1; Theresa Hauck4; Raymund E. Horch4

1Universitätsklinikum Erlangen, Plastisch- und Handchirurgische Klinik,

Forschungslabor, Erlangen, Deutschland

2Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Deutschland

3Universitätsklinikum Erlangen, Strahlenklinik, Strahlenbiologie, Erlangen,

Deutschland

4Universitätsklinikum Erlangen, Plastisch- und Handchirurgische Klinik,

Erlangen, Deutschland

Background: A promising option for reconstructing tissue defects aer

breast-conserving surgery (BCS) for breast cancer treatment is the stem-

cell-assisted lipotransfer (CAL) because of the postulated regenerative

potential of included adipose-derived stem cells (ADSCs). However,

knowledge about dierent eects of ADSCs in combination with radio-

therapy on healthy mammary cells and their microenvironment remains

incomplete.

Methods: To simulate a CAL aer BCS, an indirect coculture model

with the healthy mammary epithelial cell line MCF-10A and the human

broblast cell line MRC-5 was established. e cells were cocultured, irra-

diated with 2 and 5 Gy and treated with conditioned medium (CM) of

the ADSC cell line ASC-52telo. ereaer, the eects on transmigration

capability and on survival (ow cytometry) of MCF-10A were analyzed.

Additionally, mRNA levels of cytokines (e.g. IL1B), mesenchymal markers

(e.g. FN1) and extracellular matrix markers (e.g. MMP2) were tested.

Result: In all groups, ADSC-CM stimulated transmigration of MCF-10A.

is eect was less pronounced aer irradiation with 5 Gy. In contrast to

transmigration, ADSC-CM had no eect on survival rates.

Combined treatment with ADSC-CM and irradiation with 2 and 5 Gy

induced a higher expression of FN1 in MCF-10A. Cocultivation of MCF-

10A with MRC-5 stimulated IL1B-expression in MRC-5.

Discussion: ADSC-CM enhances transmigration of MCF-10A which

leads to the assumption of an increased cell-activity and hence a better

integration of the transplant into the mammary tissue.

Increased expression-levels of FN1 due to treatment with ADSC-CM and

irradiation can imply the induction of epithelial-mesenchymal transition

(EMT)-associated transcription changes which have to be validated by

additional testing of other EMT-markers.

Conclusion: e study shows single and combined eects of ADSCs and

radiotherapy on healthy mammary cells in their microenvironment which

should be considered in the application of CAL.

Disclosure Statement: e authors declare no conict of interest.

608

Trastuzumab deruxtecan (T-DXd) combinations in patients

with HER2-positive advanced or metastatic breast cancer: a

phase 1b/2, open-label, multicenter, dose-nding and

dose-expansion study (DESTINY-Breast07)

Hans-Christian Kolberg1; Fabrice André2; Erika Hamilton3; Sherene Loi4;

Peter Schmid5; Carey Anders6; Tinghui Yu7; Sarice Boston7; Celina D’cruz7;

Pia Herbolsheimer7; Komal Jhaveri8

1Breast and Gynecologic Cancer Center, Marienhospital, Department of

Gynecology and Obstetrics, Bottrop, Deutschland

2Goustave Roussy, Université Paris-Sud, Villejuif, Frankreich

3Sarah Cannon Research Institute/ Tennessee Oncology, Nashville, TN, USA

4Peter MacCallum Cancer Center, Melbourne, VIC, Australien

5Barts Cancer Institute, Centre for Experimental Cancer Medicine, London,

Vereinigtes Königreich

6Duke Cancer Institute, Durham, NC, USA

7AstraZeneca Pharmaceuticals, Gaithersburg, USA

8Memorial Sloan Kettering Cancer Center, New York, NY, USA

Background: HER2-targeted therapies have improved survival in patients

(pts) with HER2+ advanced/metastatic breast cancer (mBC) but chal-

lenges remain, including resistance to current HER2-targeted therapies.

In the DESTINY-Breast01 trial, T-DXd demonstrated ecacy, with an

objective response rate (ORR) of 61.4% and median progression-free sur-

vival (mPFS) of 19.4 mo in pts with previously treated HER2+ advanced/

mBC [1]. Data from an earlier cuto of this trial supported approval of

T-DXd in the US, Europe, and Japan. In a subgroup analysis of 24 pts

with stable BM, T-DXd showed preliminary ecacy, with mPFS of 18.1

mo [2]. Here, we describe a trial evaluating the safety and preliminary

antitumor activity of T-DXd monotherapy and combinations in pts with

HER2+ advanced/mBC, including pts with stable and active brain metas-

tases (BM).

Methods: DESTINY-Breast07 (NCT04538742) is a global, multicenter,

open-label, phase 1b/2 trial to evaluate the safety, tolerability, and antitu-

mor activity of T-DXd monotherapy and combinations in pts with HER2+

advanced/mBC. It consists of a T-DXd monotherapy module (0) and 5

combination modules of T-DXd plus (1) durvalumab, (2) pertuzumab, (3)

paclitaxel, (4) durvalumab + paclitaxel, or (5) tucatinib, in pts with no

or stable BM. Modules 6 (T-DXd + tucatinib) and 7 (T-DXd monother-

apy) include pts with active BM. Modules 1 - 5 each consist of 2 parts:

dose nding (part 1) and dose expansion (part 2). Modules 0, 6, and

7 include part 2 only. e primary endpoints are determination of the

recommended phase 2 doses (part 1 only) and safety and tolerability of

T-DXd and combinations (parts 1 and 2). Secondary endpoints include

ORR, PFS, PFS2, duration of response, and overall survival (part 2 only)

and pharmacokinetics and immunogenicity (parts 1 and 2).

Result: n/a

Discussion: n/a

Conclusion: n/a

Indication of source:

1. Modi, S., et al. 2021. 81(4 Supplement): p. PD3-06-PD3-06.

2. Jerusalem, G., et al. Annals of Oncology, 2020. 31: p. S63-S64.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts32

611

Feasibility of automated breast ultrasound (ABUS) for

intraoperative margin control on surgical specimens in breast

conserving surgery

Maria Eleni Hatzipanagiotou1; Deborah Huber1; Valeria Gerthofer1;

Katharina Ried1; Blanca Roca Ripoll1; Olaf Ortmann1; Stephan Seitz1

1University Medical Centre Regensburg, Department of Gynecology and

Obstetrics, Regensburg, Deutschland

Background: As breast-conserving surgery (BCS) has become stan-

dard for treatment of breast cancer, there is need for new technologies

to improve intraoperative margin assessment. Close or positive margins

during BCS lead to additional surgeries, treatment delay, additional stress

for patients, and healthcare cost. In this study we evaluated the feasibility

of ABUS to conduct specimen ultrasound in BCS.

Methods: In this monocentric, non-interventional study, specimens of 40

women who received BCS were examined via ABUS. e specimens were

xed by the surgeon on a KliniTray and put into the corresponding plas-

tic box. A construction with isotonic saline solution, gel pads and ABUS

membranes was invented to produce images of breast cancer specimens

using ABUS while avoiding contact between the transducer and the iso-

tonic water bath. Evaluation of the ABUS images was carried out by two

independent physicians trained on ABUS evaluation.

Result: In 37 (92,5%) cases the generated ABUS images were considered

of good quality by the authors. Measured tumor size with ABUS was big-

ger than with Hand-Held Ultrasound (HHUS) (mean 22,9 vs. 18,1 mm,

KI 2,38-7,35, p<0,05). e measured tumor size by ABUS was comparable

to the nal pathological tumor size (KI -0,84-4,53, p=0,17), meanwhile

there was a signicant dierence between the measured tumor size via

HHUS and pathological tumor size (KI -5,35- -1,03, p=0,005).

Discussion: e development of a method to use ABUS in specimen

ultrasound provides the opportunity to conduct further studies regarding

the accuracy of ABUS in specimen ultrasound and to evaluate whether

the generated images will be of advantage in perioperative sonography.

Conclusion: ABUS seems to be a suitable method to conduct specimen

ultrasound.

Disclosure Statement: e authors declare no conict of interest.

656

Awareness, oer, and use of psychosocial services by breast

cancer survivors in Germany – Results of the prospective

multi-centre study BRENDA II. Part 1

Susanne Singer1; Wolfgang Janni2; Felix Flock3; Ricardo Felberbaum4;

Thorsten Kühn5; Lukas Schwentner2; Elena Leinert2; Davut Dayan2;

AchimWöckel6; Tanja Schlaiß6

1University Medical Centre Mainz, Mainz, Deutschland

2Ulm, Deutschland

3Memmingen, Deutschland

4Kempten, Deutschland

5Esslingen, Deutschland

6Würzburg, Deutschland

Purpose: is study examined the pattern of psychosocial care in breast

cancer survivors.

Methods: In a prospective study with measurements before surgery, one

month, 8 months and 5 years thereaer, we examined the proportion

of breast cancer survivors who were aware about, had been oered and

received various types of psychosocial services from psychologists, social

workers, doctors, self-help groups etc. e degree of helpfulness per ser-

vice among users was ascertained. Determinants of awareness, oer and

use were investigated using binary logistic regression analyses.

Results: Among 456 breast cancer survivors who participated until 5

years, psychological services (in the hospital, rehabilitation clinic, cancer

counselling centre, private psychotherapy practice) were known by 91%,

oered to 68%, and used by 55% of patients. Social services (in the hospi-

tal, rehabilitation clinic, cancer counselling centre) were known by 86%,

oered to 65%, and used by 51%. Women ≥65 years were less likely to

be informed about (odds ratio (OR) 0.2) and get oers for psychosocial

services (OR 0.4 for social and 0.5 for psychological services) than women

<65 years. e services rated most helpful were social services in the hos-

pital, psychological counselling by a consultant and psychotherapy in pri-

vate practices.

Conclusion: ese ndings underline the importance of psychosocial

support by physicians in addition to the “professional” mental health and

social care providers. ey also show that elderly women in need for sup-

port might be in danger of not being well-informed about the services

available.

Disclosure Statement: e authors declare no conict of interest.

658

Eect of social services on nancial and role functioning

and employment in breast cancer patients with high social

burden – Results of the prospective multi-centre study

BRENDA II. Part 2

Davut Dayan1,1; Susanne Singer2; Elena Leinert1; Wolfgang Janni1;

Thorsten Kühn3; Felix Flock4; Ricardo Felberbaum5; Lukas Schwentner1;

Achim Wöckel6

1Ulm, Deutschland

2Mainz, Deutschland

3Esslingen, Deutschland

4Memmingen, Deutschland

5Kempten, Deutschland

6Würzburg, Deutschland

Background: is study examined the eects of social services (social

work care) on nancial and role functioning (work and leisure time) in

breast cancer (BC) patients 5 years aer diagnosis.

Methods: In a prospective study with analysis before surgery (t1), before

the start of adjuvant treatment (t2), aer completion of adjuvant treat-

ment (t3) and 5 years aer surgery (t4), we examined the proportion of

BC survivors with nancial or role problems and those who are employed.

We also examined how frequently social services were known about, as

well as oered and used.

Results: Of 456 BC survivors, 33% had nancial and 22% had role func-

tional problems at t4.

Of those with nancial problems, 70% were oered social services and

61% used it. Of those without nancial problems, 63% were oered coun-

seling and 60% used it. Patients with nancial problems were not more

likely to be informed about social services (odds ratio (OR) 1.1, P=0.84)

and were not more likely to use it (OR 1.3, P=0.25).

Patients with role function problems were oered social services in 73%

and used it in 61%, whereas 59% of patients without suprathreshold prob-

lems were oered it and 44% used it. Survivors with role function prob-

lems were more likely to be oered social services (OR 1.7, P=0.02) and to

use it (OR 1.6, P=0.03).

Of the 456 participants, 255 were younger than 65 years. Of these, 70%

were employed at t4. Patients with employment before surgery and who

had received social services were more likely to be employed 5 years aer

diagnosis than those without counseling (OR 1.9, p=0.04).

Conclusion: ese ndings underscore the importance of social services

among BC patients with nancial and social problems. Recipients of social

services are more likely to be employed than non-recipients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 33

721

Quality of life and therapy-adherence among breast cancer

patients: a randomized, prospective, multicenter clinical trial

on the eect of a digital software application

Heike Jansen1; Lalesu Kumas1; Wiebke Heldmaier1;

Kirsten Große Lackmann2; Anna Eichhorn1; Marko Wilhelm3;

Marion Kiechle1

1Klinikum rechts der Isar, TU München, Frauenklinik und Poliklinik, München,

Deutschland

2Spital Zollikerberg, Zollikerberg, Schweiz

3AIM - Apps in Medicine GmbH, München, Deutschland

Background: For women with breast cancer, disease and therapy come

along with loss of quality of life. Furthermore the burden of the therapy

and its side eects oen result in unauthorized discontinuation of the

therapy by patients. Non-adherence rates to endocrine therapy (ET) range

from 31% to 73% (1). Consequently these patients have a poorer progno-

sis due to recurrence, progression and cancer deaths.

Methods: We designed a randomized, prospective, multicenter clinical

trial on the eect of the use of the companion-app „Meine Busenfreundin“

on quality of life and therapy-adherence among breast cancer patients,

compared to standard of care. With validated questionnaires, patient

reported outcome monitoring data on quality of life, distress and ther-

apy-adherence are collected. In case of pathologic values, the attend-

ing breast center gets advised to intervene according to individual

requirements.

Result: Enrollment starts in 3rd quarter 2022. We expect study results in

2nd quarter 2025.

Discussion: Psychoeducation to increase therapy-adherence turned out

not to be eective. Positive eects were shown in subgroup analyses for

bidirectional communication. Moreover the use of apps with reminder

functions can increase adherence to cancer therapy. Our intention within

this project is to improve care of patients with primary breast cancer.

Conclusion: Responsible use of medical applications is a resonable com-

plement for integrative treatment: this study is conducted to show, that

side eects can be reduced and therapy-adherence increased.

Indication of source:

1 Murphy et al, Adherence to adjuvant hormonal therapy among breast cancer

survivors in clinical practice: a systematic review. Breast Cancer Res Treat.

2012 Jul;134(2):459–78.

Disclosure Statement: M. Kiechle und K. Große Lackmann sind Anteilseigner der

AIM - Apps in Medicine GmbH. Eine Forschungsförderung wurde beim Innova-

tionsfonds der Gemeinsamen Bundesausschusses beantragt.

745

Multiparametric Characterization of Circulating Tumor Cells

from Metastatic Breast Cancer Patients for Selection of

Targeted Therapies

André Franken1; Bianca Behrens2; Florian Reinhardt1; Liwen Yang1; Mahdi

Rivandi1; Ellen Honisch1; Francesco Marass3; Niko Beerenwinkel3; Irene

Esposito4; Frederic Dietzel5; Nikolas H. Stoecklein2; Dieter Niederacher1;

Tanja Fehm1; Hans Neubauer1

1Department of Obstetrics and Gynecology, University Hospital and Medical

Faculty of the Heinrich-Heine University Duesseldorf, Düsseldorf, Deutschland

2General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty

of the Heinrich Heine University Duesseldorf, Düsseldorf, Deutschland

3Department of Biosystems Science and Engineering, ETH Zurich, Basel, Schweiz

4Institute of Pathology, University Hospital and Medical Faculty of the Heinrich-

Heine University Duesseldorf, Düsseldorf, Deutschland

5Department of Diagnostic and Interventional Radiology, University Hospital

and Medical Faculty of the Heinrich-Heine University Duesseldorf, Düsseldorf,

Deutschland

Background: Over the last decades targeted therapy has become the pre-

ferred approach to treat breast cancer. However, the predictive utility of

the primary tumor is limited and obtaining serial biopsies of metastatic

lesions is challenging. us, the analysis of liquid biopsies e.g. circulating

tumor cells (CTCs) is an appealing diagnostic concept.

Methods: First, CTCs of ve metastatic breast cancer patients were

enriched with the CellSearch and analyzed by whole exome sequencing

(WES). Next, one of the patients was selected and monitored by longi-

tudinal and multiparametric liquid biopsy analyses over more than three

years, including WES, array comparative genome hybridization, RNA

proling and in vitro drug testing of CTCs.

Result: In CTCs from all patients, mutations addressable by targeted ther-

apies were detected, including mutations that were not detected in biop-

sies of the primary tumor. By further analysis of the CTCs from the index

patient, the clonal evolution of the tumor was retraced and resistance

mechanisms were analyzed. e AKT1 E17K mutation was uncovered as

the driver of the metastatic process and a chemotherapy resistant subclone

was identied. Drug testing on the patient’s CTCs conrmed the ecacy

of drugs targeting the AKT1 pathway. Based on this CTC characteriza-

tion, a targeted therapy including everolimus was selected. During this

therapy, CTC numbers dropped by 97.3% and the disease remained stable

determined by computer tomography/magnetic resonance imaging.

Conclusion: We propose that such a longitudinal and multiparametric

analysis of liquid biopsies has the potential to identify individual targets

for eective therapies, to monitor treatment response, and to optimize

the clinical outcome eventually. Furthermore, from a scientic point of

view, such studies can promote the understanding of the biology of CTCs

during dierent treatment regimens and thereby further help to optimize

treatment of all patients.

Disclosure Statement: e authors declare no conict of interest.

748

PGRMC1 binds to prohibitins upon progestin treatment and

promotes ERα activation in breast cancer cells

Nadia Stamm1; Yingxue Bai1; Marina Ludescher1; Dieter Niederacher1;

Tanja Fehm2; Hans Neubauer1

1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf,

Forschungslabor, Düsseldorf, Deutschland

2Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf,

Düsseldorf, Deutschland

Background: Women receiving combined menopausal hormone therapy

(HT) are at a higher risk for developing breast cancer (BC). e progestins

used in HT have been previously demonstrated to stimulate progesterone

receptor membrane component 1 (PGRMC1), a multifunctional protein

associated with worse survival of BC patients. Here, we describe a poten-

tial mechanism by which PGRMC1 contributes to BC progression via

estrogen receptor alpha (ERα) activation.

Methods: We investigated PGRMC1 interaction partners with special

focus on PGRMC1 phosphorylation using BC cells expressing phosphor-

ylation decient PGRMC1 variants and CRISPR/Cas9 based PGRMC1-

knockout BC cells. Since we identied PGRMC1 interaction partners

which play a role in ERα-signaling, we investigated the activation the ERα

target gene TFF1 by qPCR aer treatment of BC cells with progestins.

Further, we measured proliferation of BC cells at conditions of PGRMC1

overexpression and progestin stimulation and aer pre-treatment of cells

with the ERα-inhibitor fulvestrant.

Results: e ERα-repressors PHB1 and PHB2 were identied as inter-

action partners of PGRMC1 upon treatment with certain progestins in

BC cell lines. Further, increased interaction between PGRMC1 and PHBs

correlated with decreased binding of PHBs to ERα, indicating a contribu-

tion of PGRMC1 to the ERα-signaling network. Consequently, stimula-

tion of PGRMC1-overexpressing cell lines lead to increased proliferation

and TFF1 transcription, whereas pre-inhibition of ERα with fulvestrant

completely abolished the proliferative eect conducted by PGRMC1.

Discussion: We provide strong evidence for an involvement of PGRMC1

in activation of ERα-signaling upon treatment with certain progestins

via inhibition of the ERα-repressors PHB1 and PHB2. Subsequent ERα-

mediated oncogenic signaling increases cell proliferation and may con-

tribute to BC progression.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts34

Conclusion: Our study emphasizes the implication of PGRMC1 in the

ERα regulation network and suggests PGRMC1 as a potential therapeutic

target.

Disclosure Statement: e authors declare no conict of interest.

751

Tumour inltrating lymphocytes as prognostic factor in breast

cancer

Kathleen Schüler1; Daniel Bethmann2; Tilmann Lantzsch3;

Christoph Uleer4; Volker Hanf5; Susanne Peschel6; Jutta John7;

Marleen Poehler8; Jörg Buchmann9; Karl-Friedrich Bürrig10;

Edith Weigert11; Eva Johanna Kantelhardt1; Christoph Thomssen1;

Martina Vetter1

1Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle, Klinik

und Poliklinik für Gynäkologie, Halle (Saale), Deutschland

2Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle, Institut

für Pathologie, Halle (Saale), Deutschland

3Krankenhaus St. Elisabeth und St. Barbara, Klinik für Gynäkologie, Halle (Saale),

Deutschland

4Praxis für Gynäkologische Onkologie Uleer, Hildesheim, Deutschland

5Klinikum Fürth, Klinik für Gynäkologie

6Bernward Krankenhaus, Klinik für Gynäkologie, Hildesheim, Deutschland

7Klinikum Hildesheim, Klinik für Gynäkologie, Hildesheim, Deutschland

8Klinikum Wolfenbüttel, Klinik für Gynäkologie

9Martha-Maria Krankenhaus, Institut für Pathologie, Halle (Saale), Deutschland

10Institut für Pathologie Hildesheim, Hildesheim, Deutschland

11Pathologie Amberg, Amberg, Deutschland

Background: Tumor inltrating lymphocytes (TILs) are considered to

have prognostic and predictive value for patients with early breast can-

cer. e aim of this study was to evaluate the distribution of TILs and the

association with survival.

Methods: From a prospective, multicenter cohort of 1,270 breast can-

cer patients (PiA, Prognostic Assessment in routine application, NCT

01592825), 1,136 samples were evaluated for TIL following the recom-

mendations of the international TILs working group. TILs were grouped

(low <10%, intermediate 10-60% and high >60%) and scored as a continu-

ous parameter per 10% increment. Primary objective was the distribution

of TILs. Second objective was the association of TILs with recurrence free

interval (RFI) and overall survival (OS). e median observation time was

62 months (1-123).

Result: More than 60% TILs were detected in 1.5% of hormone receptor

(HR) positive and HER2 negative tumors, 9.7% of HER2 positive tumors

with any HR status and 18.8% of triple negative breast cancer (TNBC).

In the HER2 positive group with more than 60% TILs, no RFI event was

detected, and with less than 60% TILs, 15% of the patients had an RFI

event. e probability of OS was 94% (TILs >60%) and 81% (TILS ≤60%).

For TNBC and the same TIL cut o, 88% had no RFI and OS event, com-

pared to 70% with no event for RFI and 74% for OS. Applying 10% incre-

ments of TILs, the multivariate analysis revealed a hazard ratio of 0.89

(95% CI 0.796-1.007) for RFI and a signicant hazard ratio of 0.89 (95%

CI 0.794-0.997) for OS. A 10% increment of TILs in HER2 positive tumors

led to an increase of RFI (0.79, 95% CI 0.601-1.043) and OS (0.71, 95% CI

0.533-0.955, p<0.05) and in TNBC an increase of RFI (0.90, 95% CI 0.773-

1.063) and OS (0.94, 95% CI 0.795-1.115). ere was no eect of TILs for

patients with HR positive tumors.

Discussion: In our cohort, TILs were ascertained as an independent even

not signicant prognostic factor for patients with HER2 positive and TN

tumours.

Conclusion: TILs are a prognostic factor in breast cancer. Suitable cut os

for clinical implementation need to be found.

Disclosure Statement: e authors declare no conict of interest.

756

Correlation between single gene expression and age at

diagnosis in primary breast cancer patients

Anne-Sophie Heimes1; Walburgis Brenner1; Annette Hasenburg1;

Jan G. Hengstler2; Marcus Schmidt1

1Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und

Frauengesundheit, Mainz, Deutschland

2Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Toxikologie /

Systemtoxikologie, Dortmund, Deutschland

Background: Elderly women represent a signicant proportion of breast

cancer patients. In previous gene expression analyses we identied a sig-

nicant association between the patient’s age at surgery and certain meta-

genes, particularly immune-associated metagenes (B-cell metagene, T-cell

metagene) and the luminal metagene. In this study we analysed the cor-

relation between single genes, associated to the above mentioned meta-

genes, and patient’s age at surgery.

Methods: Using microarray-based gene expression analysis with the

Aymetrix HG-U133A array, we examined a possible correlation between

age at surgery and the expression of the single genes IGKC, CD 20 and CD

8, being associated to the B-cell and T-cell metagene respectively, in 461

breast cancer patients. Furthermore, a possible interrelation between the

ESR1 expression, as a representative single gene of the luminal metagene,

and age was investigated. Correlations were calculated using Spearman

correlation coecient.

Results: ere was a strong, signicant correlation between ESR1 expres-

sion and older age at surgery (r=0.548; p<0.001). Moreover, there was an

inverse, statistically signicant correlation between patient’s age at diag-

nosis and the above-mentioned immune-associated single genes such

as IGKC (r=-0.275; p<0.001), and CD 20 (r=-0.122; p<0.008) as part of

the B-cell metagene as well as CD 8 (r=-0.175; p<0.001), representing the

T-cell metagene.

Conclusion: Gene-expression analysis of 461 primary breast cancer

patients shows a close positive correlation between age at surgery and

ESR1 expression, whereas immune associated genes such as IGKC, CD20

and CD 8 correlate inversely with age. ese ndings should be consid-

ered when selecting the appropriate adjuvant treatment strategy.

Disclosure Statement: e authors declare no conict of interest.

769

Curcumin as a complementary approach to the Treatment of

metastatic breast Cancer

Andre Rotmann1,2

1Gynäkologisch/Onkologische Praxis, Zentrum für komplementäre Onkologie,

Rodgau, Deutschland

2Gynäkologisc/Onkologische Praxis, Zentrum für komplementäre Onkologie,

Rodgau, Deutschland

Complementery medicine is a big issue in oncological therapy in the

recent time Ecacy and safety of curcumin in combination with pacli-

taxel in patients with advanced, metastatic breast cancer: We assessed the

ecacy and safety of iv. curcumin infusion in combination with paclitaxel

in patients with metastatic and advanced breast cancer. A randomized,

double-blind, placebo-controlled, parallel-group comparative clinical

study was conducted. 150 women with advanced and metastatic breast

cancer were randomly assigned to receive either paclitaxel plus placebo

or paclitaxel plus curcumin intravenously for 12 weeks with 3 months of

follow-up. e primary outcome was determined based on the objective

response rate (ORR), as assessed by the Response Evaluation Criteria in

Solid Tumors (RECIST). e secondary outcomes were progression-free

survival (PFS), time to tumor progression (TTP), time to tumor treatment

failure (TTTF), safety, and quality of life.

Results: e intention-to-treat (ITT) analysis revealed that the ORR of

curcumin was signicantly higher than that of the placebo (51% vs. 33%,

p<0.01) at 4 weeks of follow-up. e dierence between the groups was

even greater when only patients who had completed the treatment (61%

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 35

vs. 38%, odds ratio ==2.64, p<0.01) were included. A superior eect of cur-

cumin vs placebo was observed in both patients who had completed the

treatment and all patients included in the ITT analysis, 3 months aer ter-

mination of the treatment. No other signicant dierences were observed

between the curcumin and the placebo groups, except for fatigue (3 vs. 10

patients, respectively; odds ratio ==3.7, p = 0.05). However, the patients’

self-assessed overall physical performance was signicantly higher with

curcumin than the placebo during the treatment and at the end of the

follow-up, suggesting better tolerance in the curcumin group.

Conclusions: Overall, treatment with curcumin in combination with

paclitaxel was superior to the paclitaxel placebo combination with respect

to ORR and physical performance aer 12 weeks of treatment.

Disclosure Statement: e authors declare no conict of interest.

903

Evaluation of Local Recurrence and Overall Survival

inPatients with Triple-negative Breast Cancer depending

onSurgical Procedure

Sophie Räpple1; Michael Gerken2,3; Maria Hatzipanagiotou1;

PeterUgocsai1; Monika Klinkhammer-Schalke2,3; Armin Pauer2,3;

Olaf Ortmann1; Stephan Seitz1

1Department of Gynecology and Obstetrics, University Medical Center

Regensburg, Regensburg, Deutschland

2Tumour Centre, Institute for Quality Management and Health Services

Research, Regensburg, Deutschland

3Bavarian Cancer Registry, Bavarian Health and Food Safety Authority, Regional

Centre Regensburg, Regensburg, Deutschland

Background: e primary operative therapy for triple-negative breast

cancer (TNBC) includes breast-conserving therapy (BCT) and mastec-

tomy (MXT). While data for other immunohistochemical types of breast

cancer is oen available, there is a lack of studies concerning the tri-

ple-negative subtype, that prove the long-term results and thus the onco-

logical safety of the treatment, especially aer neoadjuvant chemotherapy

(NACT). is retrospective cohort study examined the inuence of surgi-

cal intervention with or without radiation treatment on local recurrence,

overall survival and recurrence-free survival.

Methods: e study included 724 patients diagnosed with TNBC between

2010 and 2018, of whom 591 received BCT and 133 MXT. Within the

group of MXT 61 women received radiation treatment and 72 did not.

Statistical analyses were performed using IBM SPSS Statistics (version

25). e test procedures used were Chi-square independence test, Kaplan-

Meier analysis including log-rank test and uni- and multivariable Cox-

regression analysis.

Result: ere was a highly signicant advantage of BCT + RT over both

types of surgery without radiation treatment for overall survival and

recurrence-free survival in both univariable (p = <0.001; p = <0.001) and

multivariable analyses (p = <0.001; p = <0.001). In contrast no statistically

signicant dierence between the types of surgery was found for the end

point of local recurrence. e subgroup analysis of NACT presented an

advantage of BCT + RT over MXT + RT in all three end points.

Discussion: Some studies show no signicant dierences in outcomes of

local therapy but use data of treatments from the last decade. More recent

work shows consistent results but oen lacks information on local recur-

rence as an important endpoint.

Conclusion: is work provides evidence that when receiving radiation

therapy both BCT and MXT oer at least equivalent oncological safety

in TNBC. Aer undergoing NACT and radiation BCT seems not only

equivalent but superior to MXT.

Disclosure Statement: e authors declare no conict of interest.

931

Tumor Necrosis Factor-α (TNFα) Stimulate Triple Negative

Breast Cancer Stem Cells to Promote Intratumoral Invasion

and Neovasculogenesis in the Liver

Harini Narasimhan1; Francesca Ferraro1; Ralf Weiskirchen2; Elmar

Stickeler1; Jochen Maurer1

1Aachen, University Hospital Aachen RWTH, Gynecology and Obstetrics, Aachen,

Germany, Deutschland

2Aachen, University Hospital Aachen RWTH, Institut für Molekulare

Pathobiochemie, Aachen, Germany, Deutschland

Background: Triple Negative Breast Cancer (TNBC) represents the most

aggressive breast cancer subtype. Although cancer stem cells (CSCs)

are a minor fraction of all cancer cells, they are highly cancerous when

compared to their non-stem counterparts, playing a major role in tumor

recurrence and metastasis. Angiogenic stimuli and the tumor environ-

ment response are vital factors in cancer metastasis. However, cause and

eect in tumor angio- genesis and the “see-and-soil”-paradigm in TNBC

are still poorly understood.

Methods: We used primary TNBC stem cells to investigate the eect of

TNFα on. Methods include sphere forming assays, qPCR, Western Blots,

proliferation-and invasion-assays, tube formation assays, orthotopic

xenogras and immunohistochemistry.

Result: In this study we demonstrate TNFα eects on primary triple nega-

tive breast cancer stem cells (BCSCs). TNFα stimulation increased mesen-

chymality of BCSCs in an intermediate EMT state, enhanced proliferation,

self-renewal, and invasive capacity. TNFα-treatment elicited BCSC sig-

naling on endothelial networks in vitro and increased network forming

capacity of the endothelial cells. Our ndings further demonstrate that

TNFα stimulation in BCSCs has the ability to instigate distinct cellular

communication within the tumor microenvironment inducing intratu-

moral stromal invasion. Further, TNFα-treatment in BCSCs induced a

pre-metastatic niche through breast-liver organ cross talk by inducing

VCAM-1 enriched neovasculogenesis in the liver of tumor-bearing mice.

Discussion: is is the rst time the eect of TNFα induced breast-liver

organ cross talk showing increased liver neo-vasculogenesis is described

as part of a “seed-and-soil”-paradigm.

Conclusion: Overall, TNFα is an important angiogenic target to be con-

sidered in breast cancer progression to attenuate any angiogenic response

in the tumor environment which could lead to secondary organ metastasis.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts36

936

Sacituzumab govitecan (SG) versus treatment of physician’s

choice (TPC) in patients (pts) with previously treated

metastatic triple-negative breast cancer (mTNBC): Final

results from the phase 3 ASCENT study

Rudolf Weide1; Aditya Bardia2; Sara Tolaney3; Delphine Loirat4;

Kevin Punie5; Mafalda Oliveira6; Hope Rugo7; Adam Brufsky8;

Kevin Kalinsky9; Javier Cortes10; Joyce O’shaughnessy11;

Veronique Dieras12; Lisa Carey13; Luca Gianni14; Martine Piccart-Gebhart15;

Sibylle Loibl16; Yanni Zhu17; See-Chun Phan17; Sara Hurvitz18

1Praxis für Hämatologie und Onkologie, Koblenz, Deutschland

2Department of Hematology/Oncology, Massachusetts General Hospital Cancer

Center, Harvard Medical School, Boston, USA

3Medical Oncology, Dana-Farber Cancer Institute, Boston, USA

4Medical Oncology Department and D3i, Institut Curie, Paris, Frankreich

5Department of General Medical Oncology and Multidisciplinary Breast Centre,

Leuven Cancer Institute, Leuven, Belgien

6Medical Oncology Department and Breast Cancer Group, Vall d’Hebron

University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona,

Spanien

7Department of Medicine, University of California San Francisco Helen Diller

Family Comprehensive Cancer Center, San Francisco, USA

8Magee-Womens Hospital and the Hillman Cancer Center, University of

Pittsburgh Medical Center, Pittsburgh, USA

9Winship Cancer Institute, Emory University, Atlanta, USA

10International Breast Cancer Center, Quiron Group, Barcelona, Spanien

11Baylor University Medical Center, Texas Oncology, Dallas, USA

12Department of Medical Oncology, Centre Eugène Marquis, Rennes, Frankreich

13Lineberger Comprehensive Cancer Center, University of North Carolina,

ChapelHill, USA

14Medical Oncology, Gianni Bonadonna Foundation, Milan, Italien

15Medical Oncology Department, Institut Jules Bordet and l’Université Libre de

Bruxelles, Bruxelles, Belgien

16Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-

Krankenhaus, Frankfurt, Deutschland

17Department of Clinical Development, Gilead Sciences Inc, Foster City, USA

18Department of Medicine, Division of Hematology/Oncology, David Geen

School of Medicine, University of California, Los Angeles, USA

Background: Treatment goals for pts with metastatic breast cancer

include extended survival and improved quality of life (QoL). SG received

FDA approval for pts with mTNBC who received ≥2 prior chemotherapies

(at least 1 in the metastatic setting). In the pivotal phase 3 ASCENT study

(NCT02574455), SG demonstrated a signicant survival benet over sin-

gle-agent chemotherapy TPC in the primary analysis (Bardia NEJM 2021)

and QoL (Loibl ESMO 2021). With additional follow up, we present the

nal data on ecacy, including overall survival (OS), safety, and QoL.

Methods: Pts with mTNBC refractory or relapsing aer ≥2 prior chemo-

therapies with at least 1 in the metastatic setting were randomized 1:1 to

receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecit-

abine, eribulin, vinorelbine, or gemcitabine) until disease progression or

unacceptable toxicity. Primary endpoint was progression-free survival

(PFS), key secondary endpoints included OS, safety, and health-related

QoL. Safety was analyzed in pts who received ≥1 dose of study drug.

Result: At nal database lock SG (n=235) vs TPC (n=233) signicantly

improved median PFS (5.6 vs 1.7 mo; P<0.0001) and median OS (12.1 vs

6.7 mo; P<0.0001). In the safety population (n=482), key treatment-re-

lated grade ≥3 adverse events with SG (n=258) vs TPC (n=224) were diar-

rhea (11% vs 0.4%), neutropenia (52% vs 33%), anemia (8% vs 5%), and

febrile neutropenia (6% vs 2%).

Discussion: SG showed clinically meaningful and statistically signicant

improvements vs TPC in OS and QoL.

Conclusion: e analysis based on the nal database lock of ASCENT

conrms the superior survival outcomes of SG over single-agent chemo-

therapy, with a manageable safety prole and improvement in QoL for

pts with mTNBC in the 2L+ setting. ese ndings reinforce SG as an

eective treatment option for this pt population.

Indication of source:

1 Bardia et al. NEJM 2021; 384:1529-1541

2 Loibl et al. ESMO 2021; abstract 257P

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

954

The SURVIVE-study – a randomized phase 3 liquid-biopsy

based breast cancer surveillance trial

Thomas W. P. Friedl1; Sophia Huesmann1; Tatjana Braun1; Angelina Fink1;

Tanja Fehm2; Volkmar Müller3; Klaus Pantel4; Brigitte Rack1;

WolfgangJanni1

1Frauenklinik, Universitätsklinikum Ulm, Ulm, Deutschland

2Universitätsklinikum Düsseldorf, Frauenklinik, Düsseldorf, Deutschland

3Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für

Gynäkologie, Hamburg, Deutschland

4Institut für Tumorbiologie, Universitätklinikum Hamburg-Eppendorf, Hamburg,

Background: Aer patients with early breast cancer have completed pri-

mary therapy, current guidelines limit routine surveillance in breast can-

cer survivors to clinical surveillance and breast imaging. Screening for

distant metastases is initiated only in patients with specic symptoms.

Methods/Clinical Trial Design: e SURVIVE study, funded by the

German Federal Ministry of Education and Research, is a controlled phase

3 superiority trial, in which 3500 patients with intermediate-to-high risk

early breast cancer will be randomized 1:1 to guideline-based standard fol-

low-up surveillance versus intensied, liquid-biopsy guided surveillance.

Patients in the liquid-biopsy guided surveillance arm will be repeatedly

tested for the standard tumor markers CA 27.29, CA 125 and CEA, as well

as for circulating tumor cells and circulating tumor DNA. Pre-specied

abnormal ndings of any of the liquid biopsy markers indicative of mini-

mal residual disease (MRD) will trigger staging examinations including a

CT scan of the chest and abdomen and a bone scan. If the tumor staging

shows disease recurrence, the patients will receive guideline-based diag-

nostic measures and treatment; otherwise, the patients will continue liq-

uid-biopsy marker testing.

e two primary objectives of the SURVIVE study are to determine

whether the intensied, liquid-biopsy guided breast cancer surveillance

leads to a better overall survival and to assess the lead-time eect com-

pared to the standard surveillance arm. Secondary objectives include the

evaluation of invasive disease-free survival, distant disease-free survival,

quality of life, as well as sensitivity and specicity for the detection of

MRD by the liquid biopsy markers.

Result: n/a

Discussion: n/a

Conclusion: e SURVIVE study is a long-awaited breast cancer surveil-

lance trial based on promising liquid biopsy markers, which – if successful

- will lead to a paradigm shi in the current follow-up care of medium and

high-risk early breast cancer survivors.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 37

984

Tackling endocrine resistance:In vitroinvestigations

of novel ERα antagonists with a dual-target mechanism

Patricia Grabher; Nikolas Hörmann; Ronald Gust

Universität Innsbruck, Pharmazie, Pharmazeutische Chemie, Innsbruck,

Österreich

Background: 1 in 11 women in Europe is diagnosed with breast cancer

in their lifetime. Although progress has been made in the treatment of

hormone-dependent breast cancer in recent decades, intrinsic or acquired

resistances are an increasing problem. erefore, we synthetically opti-

mize known selective estrogen receptor modulators/degrader in such

a way that they target not only the common ligand binding site of the

estrogen receptor alpha (ERα) but also the co-activator binding site at the

surface of receptor with the aim of circumventing resistance mechanisms.

Methods: In-vitro investigations were carried out in hormone- dependent

MCF-7 cells, resistant and sensitive to Tamoxifen, as well as in hor-

mone-independent and ER-negative MDA-MB-231 cells. Furthermore,

we used uorine as a tracer and developed a high-resolution continuum

source electrothermal molecular absorption spectrometry (MAS) method

to quantify the intracellular drug content.

Result: We yielded IC50 values in the low µM range (IC50= 0.07- 0.5 µM)

in the wildtype MCF-7 as well as the Tamoxifen resistant MCF-7 cell line

(IC50= 0.08- 1.57 µM) and we observed no activity in the MDA-MB-231

cell line.

Discussion: For the interpretation of the intracellular eects

(ER-interaction and resulting cytotoxicity) it is necessary to know the

cellular uptake kinetic and the drug accumulation in the tumor cells.

e MAS method was validated with 5-Fluorouracil as a reference and

the results of the new ERα antagonists were correlated with inhibition of

ER-dependent transcription and observed cytotoxicity.

Conclusion: We could therefore prove that our substances are able to cir-

cumvent Tamoxifen resistance. Furthermore, as we observed no activity

in the MDA-MB-231 cell line, it indicates that we have achieved ER selec-

tivity with these substances.

Disclosure Statement: e authors declare no conict of interest.

1004

Decision-making criteria for the choice of 1st line

CDK4/6-inhibitor therapy for HR+/Her2- breast cancer

in Germany: DECISIONext

Dominique Finas1; Claudia Quiering2

1Gemeinschaftskrankenhaus Havelhöhe, Klinik für Frauenheilkunde und

Geburtshilfe, Berlin, Deutschland

2Novartis Pharma GmbH, Nürnberg, Deutschland

Purpose: AGO Breast recommendations 2021 propose endocrine-based

therapy as the 1st therapy option for HR+, MBC, if there is no threat of

organ failure. Since 11/2016, CDK4/6i plus endocrine therapy is an

option for 1st L therapy. is data collection intend to show which therapy

decisions are made and why in dierent patient groups with 1st L MBC.

Subsequent therapy may require molecular tumor characterization. How

oen molecular testing is done with MBC is largely unknown.

Methods: Retrospective data collection was carried out at 40 gynaeco-/

oncological centers in Germany. Data of 391 pts with HR+/HER2- MBC

wereanonymously recorded, treated between 01.01. and 30.06.2021 and

who’stherapy decision for a 1st L therapy was made. Questions to be

answered are:

– To what extent do dierent patient characteristics, previous treatment

and course of tumor inuence the choice of 1st L therapy?

– Factors that inuenced therapy decision?

– Frequency of molecular testing in met. situation and target parameters?

Results/Discussion: Of 391 pts, 17.4% were pre- and 82.5% postmeno-

pausal. 40.4% of the pts had de novo disease, 59.6% had (neo)adjuvant

pretreatment, 56.7% had (neo)adjuvant chemo. 36.5% of the (neo)adju-

vant treated pts relapsed during ongoing adjuvant therapy, another 8.2%

within 1 y aer completion of adjuvant therapy. Of these endocrine resis-

tant pts, treatment with CDK4/6i was not more frequent with fulvestrant

than with AI. In 32.7% of the pts, a molecular test was carried out in the

met. situation, mostly in 9.5% for PIK3CAm and in 21% for BRCAm. As

1st L therapy in the met. situation, 86.2% received a CDK4/6i, 6.6% che-

motherapy and 6.4% endocrine monotherapy. Pts on endocrine mono-

therapy are older and more likely to have solitary bone mets. Pts receiving

1st L chemotherapy are more likely to have lung and liver mets., but these

are not more likely to be symptomatic. e most common reported rea-

sons for choosing the CDK4/6i are “long experience with the substance”

(48.8%) and “data situation” (45.5%). Endocrine resistance played a role in

CDK4/6i selection in only 8% of pts.

Disclosure Statement: e authors declare no conict of interest.

1027

GeparPiPPa- A randomized, open-label, phase II trial

comparing neoadjuvant trastuzumab, pertuzumab and

endocrine therapy +/- the PI3K inhibitor inavolisib in patients

(pts) with HER2+/HR+, PIK3CA mutant early breast cancer (BC)

Sibylle Loibl1; Mattea Reinisch2; Carsten Denkert3; Andreas Schneeweiss4;

Sabine Seiler1; Peter Andreas Fasching5; Claus Hanusch6; Theresa Link7;

Vesna Bjelic-Radisic8; Jens Huober9; Michael Untch10; Christian Jackisch11;

Christine Solbach12; Jens-Uwe Blohmer13; Kerstin Rhiem14;

Thomas Büchele1; Valentina Nekljudova1; Sherene Loi15

1German Breast Group, Neu-Isenburg, Deutschland

2Evang. Kliniken Essen-Mitte, Essen, Deutschland

3Institut für Pathologie, Philipps Universität Marburg und Universitätsklinikum

Marburg (UKGM), Deutschland

4Nationales Centrum für Tumorerkrankungen, Universitätsklinikum und

Deutsches Krebsforschungszentrum, Heidelberg, Deutschland

5Universitätsklinikum Erlangen, Erlangen, Deutschland

6Rotkreuzklinikum München, München, Deutschland

7Department of Gynecology and Obstetrics, Technische Universität Dresden,

Dresden, Deutschland

8Helios Universitätsklinik Wuppertal, Universität Witten/Herdecke, Wuppertal,

Deutschland

9Kantonsspital St.Gallen, Brustzentrum, Departement Interdisziplinäre

medizinische Dienste, St. Gallen, Schweiz

10Helios Kliniken Berlin-Buch, Berlin, Deutschland

11Sana Klinikum Oenbach, Oenbach, Deutschland

12University Hospital Frankfurt, Frankfurt, Deutschland

13Gynäkologie mit Brustzentrum, Charité-Universitätsmedizin Berlin, Berlin,

Deutschland

14Zentrum Familiärer Brust- und Eierstockkrebs, Universitätsklinikum Köln, Köln,

Deutschland

15Peter MacCallum Cancer Centre, Victoria Center, Melbourne, Australien

Background: PIK3CA mutations indicate a lower response to chemo-

therapy and anti-HER2 therapy, especially in HER2+/HR+ tumors (Loibl

S 2014 and 2016). Crosstalk exists between key signaling pathways (ER,

HER2 and PI3K) and inhibition of PI3K results in the activation of HER2-

pathway (Serra V 2011). e phase III Solar-1 study demonstrated a sig-

nicant improvement in progression-free survival with the addition of

alpelisib to fulvestrant in PIK3CA mutant metastatic BC (André F 2019).

GeparPiPPa investigates the ecacy and safety of inavolisib, an oral pure

PI3Kα inhibitor, in patients with HER2+/HR+ and PIK3CA-mutated BC

in the neoadjuvant setting.

Trial design: GeparPiPPa (NCT 05306041) is a multicenter, open-label,

phase II study. 170 pts with cT1c – cT3 early BC, centrally conrmed

HER2+ and HR+-status as well as a PIK3CA tumor mutation (by NGS)

will be randomized 1:1 to receive 6 cycles of tamoxifen or an aromatase

inhibitor (1x1/d orally, day 1-21 q3w) +/- gonadotropin-releasing hor-

mone analogue plus pertuzumab/trastuzumab (subcutaneous formula-

tion [1200 (600) mg/600 mg on d1, q3w]) without or with inavolisib (9mg

1x1/d orally, day 1-21 q3w). Stratication factors are nodal status (cN0 vs

cN+) and study group (GBG vs IBCSG). Adequate organ functions and

a good performance status (ECOG PS 0-1) are required. Pts with a body

mass index >30, diabetes mellitus type I or uncontrolled type II, and/or

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts38

a history of BC within the last 5 years are excluded. Primary endpoint is

pathological complete response (pCR; ypT0/is ypN0) as determined by

core biopsy and/or denitive surgery. Secondary endpoints include com-

parison of other pCR denitions, invasive disease-free survival, overall

survival, and safety. Further (neo)adjuvant systemic treatment and radio-

therapy will be administered at the discretion of the investigator accord-

ing to standard of care.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1029

Automated prognosis marker assessment in 2’004 breast

cancers using an articial intelligence-based framework for

BLEACH&STAIN mfIHC

Tim Mandelkow1; Elena Bady1; Jan H. Müller1; Nicolaus F. Debatin1;

Magalie C. J. Lurati1; Claudia Hube-Magg1; Guido Sauter1

1Martinistraße 52, Universitätsklinikum Hamburg-Eppendorf, Pathologie,

Hamburg, Deutschland

Background: Prognostic markers in routine clinical practice of breast

cancer are currently assessed using multi-gene panels. However, the

uctuating tumor purity can reduce the predictive value of such tests.

Immunohistochemistry (IHC) holds the potential for a better risk

assessment.

Methods: To enable automated prognosis marker detection (i.e. HER2,

GATA3, PR, ER, and AR, TOP2A, Ki-67, TROP2), we have developed

and validated a framework for automated breast cancer identication,

which comprises three dierent articial intelligence analysis steps and

an algorithm for cell-distance analysis of 11+1 marker BLEACH&STAIN

multiplex uorescence immunohistochemistry (mfIHC) staining in 2’004

breast cancers.

Result: e optimal distance between Myosin+ basal cells and benign

panCK+ cells was identied as 25 µm and used to exclude benign glands

from the analysis combined with several deep learning-based algorithms.

Our framework discriminated normal glands from malignant glands

with an AUC of 0.96. e accuracy of the approach was also validated by

well-characterized biological ndings, such as the identication of 13%

HER2+, 73% PR+/ER+, and 14 triple negative cases. Furthermore, the auto-

mated assessment of GATA3, PR, ER, TOP2A-LI, Ki-67-LI and TROP2

was signicantly liked to the tumor grade (p<0.001 each). A high expres-

sion level of HER2, GATA3, PR, and ER was associated with a prolonged

overall survival (p≥0.002 each).

Conclusion: A deep learning-based framework for automated breast can-

cer identication using BLEACH&STAIN mfIHC facilitates automated

prognosis marker quantication in breast cancer.

Disclosure Statement: e authors declare the following: e PR (MSVA-570R),

the AR (MSVA-367R), the ER (MSVA-564R), the TROP2 (MSVA-733R), TOPO2A

(MSVA-802R), Myosin H11 (MSVA-375R), panCK (MSVA-000R), Ki-67 (MS-

VA-267M), GATA3 (MSVA-450M), PD-L1 (MSVA-711R) antibody clone were

provided from MS Validated Antibodies GmbH (owned by a family member

ofGS).

1032

Evaluation of the Age Limits of Mammography Screening in

Germany – A Decision-Analysis to Inform Decision Making

based on Long-Term Benets and Harms

Gaby Sroczynski1; Lara Hallsson1; Nikolai Mühlberger1; Felicitas Kühne1;

Beate Jahn1,2; Heike Kölsch3; Stefan Sauerland3; Konstanze Angelescu3;

Uwe Siebert1,2,4,5

1Institute of Public Health, Medical Decision Making und Health Technology

Assessment, UMIT - University for Health Sciences, Medical Informatics and

Technology, Hall i. T., Österreich

2Division of Health Technology Assessment, ONCOTYROL Center for

Personalized Cancer Medicine, Innsbruck, Österreich

3Institute for Quality and Eciency in Health Care (IQWiG), Cologne,

Deutschland

4Center for Health Decision Science, Departments of Epidemiology and Health

Policy & Management, Harvard T. H. Chan School of Public Health, Boston, USA

5Institute for Technology Assessment and Department of Radiology,

Massachusetts General Hospital, Harvard Medical School, Boston, USA

Background: In Germany, the organized breast cancer (BC) screen-

ing program includes biennial mammography for women in the age of

50-69 years. We evaluated the long-term benets and harms of various

BC screening strategies including mammography with earlier start and/or

later stop at dierent screening intervals.

Methods: We developed a Markov-state-transition model simulating BC

progression including ductal carcinoma in situ (DCIS) to evaluate various

screening strategies diering by age at start and end of screening and by

screening interval. International data for mammography accuracy along

with German epidemiologic, clinical data and age-specic quality-of-life

(QoL) data were used. Outcomes included detected DCIS and invasive

BC, BC-related deaths, life years [LY], and quality-adjusted LY (QALY),

number of positive, false-positive, and total mammograms, overdiagnosis,

and the incremental harm-benet ratio (IHBR). Comprehensive sensitiv-

ity analyses were conducted.

Result: In the base-case analysis, the highest gain in LY was achieved

with mammography at age 45–79 (annual, age 45–49y; biennial, 50–79y)

with 10.0 LY gained [LYG] per 100 participating women compared with

current screening. e highest gain in QALYs is expected by biennial

mammography at ages 45–74 (3.5 QALYs gained/100 women vs. current

screening). Lowering the start age to 45 years (biennial, age 45–69y) has

an IHBR of 47 additional mammograms/LYG (vs. current screening).

Compared to this screening, additionally extending mammography to 74

years (biennial, age 45–74y) results in 96 additional mammograms/LYG.

Annual screening at age 45–49 or extending biennial screening to age

79 results in substantially less favorable IHBRs. Overdiagnoses occurred

mainly due to DCIS. Key results were robust in sensitivity analyses.

Conclusion: Based on our results, extension of the starting and stopping

age for mammography may prevent additional BC deaths and increase

remaining life expectancy. Considering QoL, biennial screening from age

45 to 74 years provides an acceptable benet-harm balance.

Disclosure Statement: e authors declare the following: is work was con-

ducted and funded within a benet assessment of the Institute for Quality and

Eciency in Health Care (IQWiG) commissioned by the Federal Joint Committee

(G-BA).

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 39

1059

MINERVA - Combination of Abemaciclib and endocrine

therapy in hormone receptor positive (HR+) HER2 negative

(HER2-) locally adv./metastatic breast cancer with focus on

digital side eect management

Brigitte Rack1; Natalie Uhl1; Kristina Veselinovic1; Amelie Degregorio2;

Thomas W. P. Friedl1; Kerstin Pster1; Angelina Fink1; Tanja Fehm3;

Jens Huober4; Wolfgang Janni1

1University Hospital Ulm, Department of Gynecology and Obstetrics, Ulm,

Deutschland

2SLK-Kliniken, Heilbronn, Department of Gynecology and Obstetrics, Heilbronn,

Deutschland

3Heinrich-Heine-University Düsseldorf, Department of Gynecology and

Obstetrics, Düsseldorf, Deutschland

4Kantonsspital St.Gallen, Breast Unit, St. Gallen, Schweiz

Background: Systematic collection of self-assessed Patient-Reported

Outcome (PRO) has gained increasing interest in clinical oncology.

Clinical monitoring of PROs via digital application tools oers signicant

benets. Patient reported side eects enable early intervention or treat-

ment adaption leading to reduced toxicity and increased quality of life

(QoL), as well as earlier detection of progressive disease (PD) or lack in

treatment eectiveness.

Clinical Trial Design/Methods: e MINERVA study is designed as an

open-label, non-randomized, phase IV trial to assess the ecacy and

safety of the CDK 4/6 inhibitor Abemaciclib plus endocrine therapy in

300 women with HR+HER2- advanced/metastatic breast cancer in a rst

line setting with focus on digital side eect management.

MINERVA oers a mandatory use of CANKADO Pro-React, a digital

health application to support therapy management and physician-patient

interaction. is includes a patient diary for daily documentation of can-

cer-/treatment-related symptoms as well as frequent QoL-questionnaires

(EORCT-QLQ-C30 and BR23). An integrated algorithm detects early

symptom deteriorations, triggers alert notications and gives recommen-

dations for timely symptom management. Patient-specic reports support

the preparation of patient visits and monitoring of patient compliance. A

translational research project will aim to identify markers for endocrine

treatment resistance.

e primary objective of this trial is the estimation of progression

free survival (PFS) from date of registration until PD or death. Secondary

objectives include the evaluation of adverse events and additional cap-

ture of Patient-Reported side eects on a daily basis via CANKADO

PRO-React.

Result: n/a

Discussion: n/a

Conclusion: e MINERVA study investigates the eectiveness and safety

of an endocrine-based therapy in combination with Abemaciclib with a

focus on digital side eect management and will lead to further insights

regarding safety, tolerability and QoL of this treatment regimen.

Disclosure Statement: e authors declare the following: Financial Disclosure

Cancer of Unknown Primary (CUP)

Poster

223

Baseline mutational proles of patients (pts) with carcinoma-

of-unknown-primary-origin (CUP) enrolled onto CUPISCO

Benedikt Westphalen1; Armen R. Karapetyan2; Andreas Beringer2;

Tilmann Bochtler3; Nassera Chalabi2; Natalie Cook4;

Gonzalo Duran-Pacheco2; Sophie Golding2; Elen Hoglander2; Ferran Losa5;

Linda Mileshkin6; Holger Moch7; Chantal Pauli7; Jerey S. Ross8,9;

Ethan S. Sokol8; Richard W. Tothill10; Alwin Krämer3

1Comprehensive Cancer Center Munich, Ludwig Maximilian University of

Munich, Department of Medicine III, Munich, Deutschland

2F. Homann-La Roche Ltd, Basel, Schweiz

3Deutsches Krebsforschungszentrum, Heidelberg, Deutschland

4The University of Manchester, The Christie NHS Foundation Trust, Manchester ,

Vereinigtes Königreich

5Hospital de Sant Joan Despí Moisès Broggi, ICO-Hospitalet, Barcelona, Spanien

6Peter MacCallum Cancer Centre, Melbourne, Australien

7Universitätsspital Zürich, Institut für Pathologie und Molekularpathologie,

Zürich, Schweiz

8Foundation Medicine Inc, Cambridge, USA

9SUNY Upstate Medical University, Syracuse, USA

10University of Melbourne, Department of Clinical Pathology, Parkville,

Australien

Background: NCCN guidelines consider next-generation sequencing

important in guiding therapeutic decision-making in CUP. CUPISCO

(NCT03498521) is an ongoing, phase II randomised study of targeted

therapy/cancer immunotherapy vs platinum-based chemotherapy in

pts with unfavourable CUP, dened per ESMO guidelines. We present a

descriptive molecular analysis of ~50% of pts designated for enrolment.

Methods: Comprehensive genomic proling, including determination of

microsatellite instability (MSI) and tumour mutational burden (TMB),

was performed on formalin-xed, paran-embedded tissues using the

F1CDx assay. Gene alterations (GAs) found in ≥3% of pts were analysed

using multiple correspondence analyses and hierarchical clustering to

identify co-occurrences.

Result: Median age was 61.5 years (n = 346 [Apr 2021]; range: 22–84);

median TMB was 2.5 mut/Mb (0–63.0). Most frequent GAs were TP53

(44%), CDKN2A (32%), KRAS (21%; 2% G12C), CDKN2B (21%),

ARID1A (13%), STK11 (13%), MTAP (12%), PIK3CA (10%), MYC (8%),

PBRM1 (8%), BAP1 (8%) and FGFR2 (8%). Beyond PIK3CA and FGFR2,

other targetable GAs were identied in EGFR (2%), ERBB2 (6%), ALK

(0.3%), ROS1 (1%), MET (2%), NTRK1 (1%) and BRAF (6%). e fre-

quency of MSI-high and TMB-high (>16 mutations/Mb) samples was 3%

and 9% respectively. Based on hierarchical clustering of co-mutational

proles, multiple clusters were identied, each characterised by specic

GA co-occurrences.

Discussion: In our analysis, 30% of patients carried a potentially targeta-

ble GA, shedding light on the molecular landscape in pts with poor-prog-

nosis CUP. Our analyses demonstrate that CUP cases can be clustered

based on molecular proling; further studies are needed to determine if

these clusters carry clinical relevance.

Conclusion: Our early results suggest that comprehensive genomic prol-

ing of CUP samples identies therapeutically relevant GAs in a signicant

proportion of patients and could thus guide personalised treatment.

Previously presented atESMO2021,“FPN:1804P,C. Benedikt Westphalen

et al.”Reused with permission.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts40

261

Relevance of the time interval between surgery and adjuvant

radio (chemo) therapy in HPV-negative and advanced head

and neck carcinoma of unknown primary (CUP)

Matthias Balk1; Robin Rupp1; Konstantin Mantsopoulos1; Moritz Allner1;

Philipp Grundtner1; Sarina Müller1; Maximilian Traxdorf1;

Markus Eckstein2; Stefan Speer3; Sabine Semrau3; Rainer Fietkau3;

Heinrich Iro1; Markus Hecht3; Antoniu-Oreste Gostian1

1Hals-Nasen-Ohren-Klinik, Kopf- und Halschirurgie, Friedrich-Alexander

Universität Erlangen-Nürnberg, Erlangen, Deutschland

2Pathologisches Institut, Friedrich-Alexander Universität Erlangen-Nürnberg,

Erlangen, Deutschland

3Strahlenklinik, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen,

Deutschland

Background: e eect of therapy duration in HNSCC-CUP has not

been thoroughly investigated, thus this study aimed to assess as primary

objective the impact of the time range between surgery and adjuvant ther-

apy on the oncologic outcome, in particular the overall survival (OS), in

advanced staged, HPV negative CUP at a tertiary referral hospital. Disease

specic survival (DSS) and progression free survival (PFS) are dened as

secondary objectives.

Methods: Between January 1st, 2007, and March 31st, 2020 a total of 131

CUP- patients were treated. Out of these, 59 patients with a conrmed

negative p16 analysis were referred to a CUP-panendoscopy with simulta-

neous unilateral neck dissection followed by adjuvant therapy. e cut-o

between tumor removal and delivery of adjuvant therapy was set at the

median of 55 days (d; 95% CI 51,42-84,52), i.e. 30 patients received adju-

vant therapy within 55 d (mean 41.69 d, SD=9.03) aer surgery in contrast

to 29 patients at least aer 55 d (mean 73.21 d, SD=19.16).

Result: e mean follow-up time was 43.6 months (SD=36.7 months).

Regarding all patients, the OS was 71% (95% CI 0.55-0.86). Patients

receiving adjuvant therapy < 55 d (77%, 95% CI 0.48-1.06) had compara-

ble OS compared to those ≥ 55 d (64%, 95% CI 0.42-0.80; X2(1) =1.16, p =

0.281). e DSS of all patients was 86% (95% CI 0.75-0.96). For the group

< 55 d it was 95% (95% CI 0.89-1.01) compared to the group ≥ 55 d with

76% (95% CI 0.57-0.95; X2(1) =2.32, p = 0.128). e PFS was 72% (95% CI

0.59-0.85). In the group < 55 d it was 78% (95% CI 0.63-0.94) and thus not

signicantly dierent from 65% (95% CI 0.45-0.85) of the group ≥ 55 d;

X2(1) =0.29, p = 0.589).

Conclusion: e results presented suggest that the oncologic outcome of

patients with advanced, HPV-negative HNSCC-CUP is not aected by

an extended time between surgery and adjuvant therapy. Consequently,

patients with advanced CUP may still benet from delayed adjuvant

therapy.

Disclosure Statement: e authors declare no conict of interest.

Cancer Prevention

Best-of-Abstract-Vortrag

102

HaSCo Study: First results of a pilot study for systematic

HPV self-sampling for non-responders to the cervical cancer

screening program

Matthias Jentschke1; Sophia Groß1; Stephanie Hempel1;

Lena Steinkasserer1; Barbara Neuhaus2; Siegfried Geyer3; Armin Koch4;

Peter Hillemanns1

1Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule

Hannover, Hannover, Deutschland

2Zentrum für klinische Studien, Medizinische Hochschule Hannover, Hannover,

Deutschland

3Medizinische Soziologie, Medizinische Hochschule Hannover, Hannover,

Deutschland

4Institut für Biometrie, Medizinische Hochschule Hannover, Hannover,

Deutschland

Background: In this pilot study we evaluate a systematic approach

towards human papillomavirus (HPV) self-sampling for non-responders

to the German cervical cancer screening program. In 2020, the renewed

organized screening program with co-testing (HPV test + cytology) in

3-yearly intervals was started for all women 35 years and older. In the past,

the participation rate was around 70% in a time frame of three years. e

non-participators are at higher risk to develop invasive cervical cancer.

e willingness to participate can be improved by oering self-sampling

devices for home-based use. Based on this information, the Hannover

Self-Collection study was started to examine the response rate and practi-

cability of a systematic self-sampling approach.

Methods: 20.000 women aged 30 to 65 years living in the city and region

of Hannover, Lower Saxony were randomly included. 10.000 women

directly received a self-sampling kit, the other 10.000 a letter of informa-

tion and option to participate in the study (opt-out vs. opt-in strategy).

Stratications were be made by age (7 cohorts) and area of living (city vs

rural). Women tested positive for high-risk HPV (PCR-based HPV assay)

were prompted to get a cytological smear by their gynecologist. Women

with normal cytology will be re-checked aer 6 months. Suspicious cytol-

ogy results lead to an immediate colposcopy.

Results: e study is executed between December 2021 and May 2022.

First results will be presented at the congress.

Discussion and Conclusions: To get hold of non-responders to cervical

cancer screening programs, self-sampling for HPV is a promising option.

Aim of this study is to generate an overall recommendation to improve

cervical cancer screening in Germany, especially for non-responders. is

study is supported by Deutsche Krebshilfe.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 41

852

A Randomized Trial of Risk-Adapted Screening for Prostate

Cancer in Young Men – Updated Results of the First Screening

Round of the PROBASE Trial

Peter Albers1,2; Christian Arsov1,3; Jale Lakes1; Jan Philipp Radtke1;

Kathleen Herkommer4; Jürgen Gschwend4; Inga Peters5; Markus Kuczyk5;

Stefan Koerber6; Jürgen Peter Debus6; Boris Hadaschik7; Glen Kristiansen8;

Lars Schimmöller9; Gerald Antoch9; Ernst Rummeny10; Marcus Makowski10;

Frank Wacker11; Heinz Schlemmer12; Axel Benner13; Roswitha Siener14;

Rudolf Kaaks15; Nikolaus Becker16

1Department of Urology, Medical Faculty, Heinrich-Heine University Düsseldorf,

Düsseldorf, Deutschland

2Division of Personalized Early Detection of Prostate Cancer, German Cancer

Research Center (DKFZ), Heidelberg, Deutschland

3Department of Urology, Städtische Kliniken Mönchengladbach,

Mönchengladbach, Deutschland

4Department of Urology, Technical University Munich, Deutschland

5Department of Urology, Medical University Hannover (MHH), Hannover,

Deutschland

6Department of Radiooncology, University Hospital Heidelberg, Heidelberg,

Deutschland

7Department of Urology, University Hospital Essen, Essen, Deutschland

8Department of Pathology, University Hospital Bonn, Bonn, Deutschland

9Institute of Diagnostic and Interventional Radiology, University Hospital

Düsseldorf, Department of Urology, Düsseldorf, Deutschland

10Institute of Radiology, Technical University Munich, München, Deutschland

11Institute of Radiology, Medical University Hannover (MHH), Hannover,

Deutschland

12Institute of Radiology, German Cancer Research Center (DKFZ), Heidelberg,

Deutschland

13Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg,

Deutschland

14Department of Urology, University Hospital Bonn, Bonn, Deutschland

15Division of Cancer Epidemiology, German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

16Division of Personalized Early Detection of Prostate Cancer, German Cancer

Research Center (DKFZ), Heidelberg, Deutschland

Background: Prostate-specic antigen (PSA) – based screening has

proven to signicantly reduce prostate cancer (PCa) mortality. However,

population-based screening for PCa suers from a high rate of overdiag-

nosis followed by overtreatment. A digital rectal examination (DRE) still

represents the mainstay of the German statutory early detection program.

In contrast, risk-adapted approaches have been suggested to improve the

accuracy. Here we report on updated results of the risk-adapted PROBASE

screening trial for PCa aer the rst screening round.

Methods and Participants: From February 2014 to December 2019,

PROBASE recruited and randomized 46,642 men in Germany at age 45

to receive either an immediate PSA test (arm A) or a delayed PSA test at

age 50 (arm B). Participants in arm B were oered a DRE at the time of

enrolment instead of a PSA test. PSA tests classied participants in arm A

into a low (<1.5 ng/ml), intermediate (1.5-2.99 ng/ml) or high (>3 ng/ml)

risk category. In cases of conrmed PSA values >3 ng/ml participants were

recommended a prostate biopsy based on upfront multiparametric mag-

netic resonance imaging.

Results: Baseline PSA tests categorized the 23,301 participants of arm

A into low (89.2%) and intermediate (9.3%) risk. With conrmed PSA

>3ng/ml 186 (0.8%) men were at high risk of whom 120 (64.5%) under-

went a biopsy with detection of 48 prostate cancers (overall prevalence

0.2%). Only four patients had International Society of Uropathology

(ISUP) grade group (GG) > 3 cancers (overall prevalence 0.02%). In arm

B, 23,194 participants were enrolled and 6,537 underwent a DRE with 57

suspicious ndings. Two of which showed ISUP GG 1 PCa corresponding

to a detection rate by DRE of 0.03% (2/6,537).

Discussion and Conclusion: e majority of men (about 90%) at age 45

presents with a PSA below 1.5 ng/mg which implies a very low risk to

develop prostate cancer. e prevalence of screen-detected clinically sig-

nicant PCa in 45-year-old men is very low. Moreover, the rate of aggres-

sive cancers (ISUP GG 3-5) is even lower. DRE did not turn out eective

for early detection of PCa.

Disclosure Statement: e authors declare no conict of interest.

Poster

451

Changes in modiable life style factors in women

with an increased hereditary risk for breast and ovarian

cancer during the SARS-CoV-2 pandemic in Germany:

A cross-sectional web-based survey

Roxana Schwab; Annika Droste; Annette Hasenburg

University Medical Center Mainz, Department of Gynecology and Obstetrics,

Mainz, Deutschland

Background: Pathogenic mutations in BRCA1 and BRCA2 are associated

with high risks of breast (BC) and ovarian cancer (OC). Modiable life

style factors are important in explaining some of the variation in cancer

risks in both, OC and BC. Crucial steps to prevent malignant disease are

increased physical activity, avoidance of smoking, limitation of the intake

of red meat or alcohol.

Methods: To assess possible changes in life style, a web-based survey was

placed on internet platforms of patients´ support groups between 29th

January and 22th April 2021. Missing data were composed of those patients

who did not answer the question or who did not have a clear opinion

regarding the topic. Data are presented as frequencies of selected items.

Group dierences were calculated by χ2-test.

Result: During the pandemic, 10.5% of respondents consumed signi-

cantly more or more alcohol, while 31.6% consumed less or signicantly

less alcohol than before the pandemic. With respect to abuse of nico-

tine, 11.8% consumed more and 17.6% consumed less than before the

pandemic. 16.2% engaged in signicantly more or more physical activ-

ity, whereas 47.1% engaged in less or signicantly less physical activity,

respectively. 8.7% stated that they maintained a healthy body weight,

while 17.4% did not. A healthy diet was strictly observed or observed by

13.9% of respondents, while 23.6% observed a healthy diet less or signi-

cantly less than before the pandemic.

Discussion: e exact impact of life style changes during the SARS-CoV-2

pandemic on cancer (recurrence) risk, as well as on subsequent survival,

is still unknown, but it has the potential to lead to important public health

implications in the coming years.

Conclusion: us, especially during challenging periods of life, women

at high risk for cancer occurrence or recurrence should be reassured that

observing a healthy lifestyle (healthy diet, control of obesity, decreased

smoking etc.) is an excellent option for cancer prevention and increased

survival.

Disclosure Statement: e authors declare the following:

RS: Honoraria: Roche Pharma AG, AstraZeneca, Streamedup!GmbH AH: Hono-

raria: AstraZeneca; Celgen; MedConcept GmbH, Med update GmbH; Medicultus;

Pzer; Promedicis GmbH; Soconsult; Roche Pharma AG; Streamedup!GmbH;

Tesaro Bio Germany GmbH, LEO Pharma Ad Board: PharmaMar; Promedicis

GmbH; Roche Pharma AG; Tesaro Bio Germany GmbH, AstraZeneca, LEO

Pharma, MSD Sharp & Dohme GmbH

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts42

570

Impact of a German campaign promoting physical activity

against cancer on physical activity levels

Dimitra Theoklitou; Freerk T. Baumann

Uniklinik Köln, Klinik I für Innere Medizin, Centrum für Integrierte Onkologie

Aachen Bonn Köln Düsseldorf, Köln, Deutschland

Abstract: Purpose: e instrumental role of physical activity in the pri-

mary prevention of cancer is indisputable. e current study aimed

to evaluate the success of the information campaign “Physical activity

against cancer” in Germany.

Methods: A total of 2,003 telephone interviews were conducted using two

telephone surveys (September 2013, n=1,000; September 2014, n=1,003)

among randomly chosen participants aged 18 years or older using the

Global Physical Activity Questionnaire (GPAQ). Questions aimed at

assessing the accessibility of the campaign and its impact on physical

activity levels and the knowledge of the participants regarding the relation

between physical activity and cancer prevention.

Results: Results showed that 27% of participants of the second survey had

heard about the campaign. e metabolic equivalent task (MET) scores

in total and for the physical activity from transportation for those who

were exposed to the information compared to the rest interviewees were

associated with statistically signicant eects.

Discussion: e campaign “Physical activity against cancer” had a suc-

cessful impact on the increment of the physical activity levels of the par-

ticipants who were exposed to the information of the campaign and can

be considered as a motivator for people to become physically more active.

According to the results of both surveys, there is an excess of knowledge

among the respondents that regular physical activity can have an impact

on the cancer risk reduction, which can play an important role in cancer

prevention.

Conclusions: Information campaigns and education can have an inu-

ence on changing people’s movement behavior. e question remains

whether these observations are possibly associated with cancer in partic-

ular and are therefore dicult to transfer to other diseases. Methodical

limitations were that this was a cross sectional study and the missing con-

trolled intervention exercise program.

Disclosure Statement: e authors declare no conict of interest.

724

Pilot project: Easily said and done: Prevention and early

detection of colon cancer and skin cancer

Sandra Bothur1; Inga Knapp2; Friederike Kreuzwieser1; Martin Schieron3;

Tanja Segmüller3

1Krebsgesellschaft Nordrhein-Westfalen e.V., Düsseldorf, Deutschland

2Kompetenzzentrum Barrierefreiheit Volmarstein, Wetter (Ruhr), Deutschland

3HS Gesundheit Bochum - Hochschule für Gesundheit, Department of

Community Health, Bochum, Deutschland

Background: Colon cancer is the second most common cancer in women

and third most common in men in Germany - black skin cancer is the

fourth most common cancer in women and h in men. Studies show

that persons with so-called intellectual disabilities use cancer screening

programs less than the average population. It can be assumed that the

usual information material on cancer prevention and care do not reach

these persons adequately.

Methods: e information must be made available and disseminated in

such a way that it reaches the target audience. e project takes a partici-

patory approach, involves various stakeholders and asks people from the

target group themselves about their information needs and ways of obtain-

ing information. e content was developed in focus groups and surveys

of the target groups on image and training design were implemented.

Result: Easy to read language can help to achieve accessible communi-

cation for people with learning diculties. is refers to both written

information (e.g. information brochures) and oral communication (e.g.

conversation with a doctor). Self-determination and participation can

only succeed if information reaches the person. is means: All the nec-

essary information must be available and conveyed in easy language.

Analogue and digital media were developed in a participatory manner to

support doctor-patient-communication.

Discussion: Overall, these persons have diverse, multifaceted problems

with health care. For example, in many cases individual initiative and

responsibility is necessary to participate in an examination. is is not

always the case for people with so-called intellectual disabilities. eir

previous experiences in the health sector and the relationship with the

doctor, which can oen be disturbed by communication diculties, also

play an important role.

Conclusion: e project is an important contribution to improving health

communication for people with so-called learning diculties and medical

professionals.

Disclosure Statement: e authors declare no conict of interest.

940

Evaluation of HPV-vaccination campaigns in Germany: Reach

of target groups and impact on vaccine uptake willingness

Catharina Maulbecker-Armstrong1; Karin Moser1; Nobila Ouedraogo2

1Fachbereich Gesundheit, Technische Hochschule Mittelhessen, Gießen,

Deutschland

2Deutsches Krebsforschungszentrum, Krebsprävention, Heidelberg,

Deutschland

Background: German population is poorly informed about the HPV-

vaccination and its health benets. is is shown by the low vaccination

rates (2019: girls 47.2%, boys 5.1%). Despite educational information pro-

vided by German Federal Centre for Health Education (BZgA) over years,

progress in HPV-vaccination rate is still low. us, existing communica-

tion strategies on HPV-vaccination need to be evaluated and adapted if

necessary.

Methods: We aim to evaluate a nation-wide HPV campaign planned by

the manufacturer of the HPV vaccine Gardasil with regards on the reach

of the target groups (parents, teens, students) and the impact on vaccine

uptake willingness. Surveys will be carried out in the target groups for

this purpose. In this work a rst survey with parents from children in

class 3 to 6 is planned and a second one for adolescents at the age of 15-16

years. A third survey will be performed among students of the Technische

Hochschule Mittelhessen (THM). In all cases we want to analyze how

informed the respective group is, if they are vaccinated or if they are will-

ing to get vaccinated themselves or in the case of the parents to let their

children be vaccinated.

Result: We expect an increase in HPV-vaccination uptake or in willing-

ness to get vaccinated among target groups exposed to the campaign and

to learn about additional alternate communication channels.

Discussion: To increase the HPV-vaccination rate, it is crucial to ade-

quately inform the population. Parents and adolescents can decide and

act appropriately only if they are aware of the risk of an HPV-infection.

Information can happen through campaigns, by pediatricians, family

doctors and through events at schools. Classic communication channels

are not as attractive for adolescents. To reach them, their channels (e.g.

opinion-vlogger or YouTuber as role models) have to be used. Vaccination

rates can only increase if all target groups are both reached through their

respective Channels and informed.

In collaboration with the Allianz gegen HPV

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 43

941

Lost cohorts in the HPV vaccination due to the covid-19

pandemic and potential eects on future HPV associated

cancers

Catharina Maulbecker-Armstrong1; Karin Moser1; Nobila Ouedraogo2

1Fachbereich Gesundheit, Technische Hochschule Mittelhessen, Gießen,

Deutschland

2Deutsches Krebsforschungszentrum, Krebsprävention, Heidelberg,

Deutschland

Background: Due to covid-19 pandemic, the lock downs and long home-

schooling periods children /adolescents and their parents were neither

reachable for school personnel nor for healthcare professionals. erefore,

vaccination rates decreased by 14% for girls and 9% for boys (DAK Kinder-

und Jugendreport 2021). Consequently, children in the target age of 9 to

14 years were lost for the HPV-vaccination. A 2-dose-vaccination-scheme

is used for children younger than 15 years. Older kids need 3 vaccinations

for a complete immunization. e GKV generally reimburses only the

cost for age groups younger than 18 years. We aim to assess the resulting

HPV associated treatment cost in the German healthcare system and to

develop a proposal on how to get the lost cohorts vaccinated.

Methods: To assess the additional cost related to the decrease in vacci-

nation rates, we plan to use the following approaches: Scenarios analysis

of the need of the 3-dose-scheme (Vaccine, organization, personnel) and

future HPV related treatment costs. We will conduct expert interviews

and compare sales gures of Gardasil with data from the KV. Finally, we

compare European / international countries, on how do they organize the

catch-up for the lost cohorts.

Result: We expect increasing costs due to a third vaccination regime and

the treatment of HPV related cancers based on missing immunizations in

the juvenile age.

Discussion: An increased nancial burden will be result in the future, if

Germany fails to catch-up the lost children and adolescents based on the

HPV vaccination gap due to the pandemic. Mechanisms need to be in

place to include adolescents, i.e. through the J1-exami, for the catch-up

vaccinations. Alternatively, the age limit for a reimbursement could be

raised for a limited period of time to immunize the young adults between

18 and 20 years.

In collaboration with the Allianz gegen HPV

Disclosure Statement: e authors declare no conict of interest.

975

The role of tobacco smoking in the ecacy of brief alcohol

intervention: Results from a randomized controlled trial

Filipa Krolo1,2; Sophie Baumann3; Anika Tiede1,2; Kristian Krause1;

Christian Meyer2,4; Gallus Bischof5; Ulrich John2,4; Beate Gärtner6;

Jennis Freyer-Adam1,2

1Institut für Medizinische Psychologie, Universitätsmedizin Greifswald,

Greifswald, Deutschland

2Deutsches Zentrum für Herz-Kreislauf-Forschung, Standort Greifswald,

Greifswald, Deutschland

3Institut für Präventionsforschung und Sozialmedizin, Universitätsmedizin

Greifswald, Abteilung für Methoden der Community Medicine, Greifswald,

Deutschland

4Institut für Präventionsforschung und Sozialmedizin, Universitätsmedizin

Greifswald, Institut für Community Medicine, Greifswald, Deutschland

5Klinik für Psychiatrie und Psychotherapie, Universität Lübeck, Lübeck,

Deutschland

6Robert-Koch-Institut Berlin, Abteilung für Epidemiologie und

Gesundheitsmonitoring, Berlin, Deutschland

Purpose: Tobacco smoking and at-risk alcohol consumption are among

the most important modiable risk factors for cancer morbidity and

-mortality. is study investigated whether current tobacco smoking

moderates the ecacy and the comparative ecacy of in-person and

computer-based brief alcohol interventions in at-risk alcohol drinking

general hospital patients.

Methods: As part of a randomized controlled trial funded by Deutsche

Krebshilfe, 961 general hospital patients aged 18-64 years, were allocated

to in-person counseling (PE), computer-generated individual feedback

(CO) and assessment only. PE and CO included contacts at baseline, 1

and 3 months later. Aer 6, 12, 18 and 24 months, self-reported reduc-

tion of alcohol use per day was assessed as outcome. Using latent growth

curve models, self-reported current smoking status (yes/ no) and number

of cigarettes per day were tested as moderators of brief alcohol interven-

tion ecacy.

Results: In PE and CO, study participants reduced their alcohol use inde-

pendently of their smoking status over 24 months (ps <0.005). At month

24, neither smoking status nor number of cigarettes per day moderated the

ecacy and the comparative of PE and CO (ps >0.05). Up to month 12,

and among persons smoking 19 cigarettes per day or less, ecacy of CO

increased signicantly with increasing number of cigarettes (ps <0.05).

Discussion: Although in the short-term, heavier smokers with a maxi-

mum of 19 cigarettes per day, might benet more from CO relative to

assessment only than light smokers, smoking status and heaviness of

smoking did not interfere with intervention ecacy in the long-term.

Conclusion: For the purpose of screening and brief alcohol intervention

in medical practice, our ndings indicate that tobacco smoking does not

interfere with the ecacy of brief alcohol interventions, whether delivered

in-person or computer-based.

Disclosure Statement: e authors declare no conict of interest.

1022

Proactive Automatized Lifestyle intervention for cancer

prevention (PAL) and reach of general hospital patients

Jennis Freyer-Adam1; Marie Spielmann1; Filipa Krolo1; Anika Tiede1;

Kornelia Sadewasser1,2; Christian Meyer3; Gallus Bischof4; Ulrich John3

1Institut für Medizinische Psychologie, Universitätsmedizin Greifswald,

Greifswald, Deutschland

2Deutsches Zentrum für Herzkreislauorschung, Greifswald, Deutschland

3Institut für Präventionsforschung und Sozialmedizin, Universitätsmedizin

Greifswald, Greifswald, Deutschland

4Abteilung für Psychiatrie und Psychotherapie, Medizinische Universität zu

Lübeck, Lübeck, Deutschland

Purpose: Multiple health risk behaviors (HRBs, i.e. tobacco smoking,

at-risk alcohol use, physical inactivity and unhealthy diet) more than dou-

ble the risk of cancer, and apply to more than half of the adult popula-

tion. Targeting multiple HRBs should be in the focus of cancer prevention

research. Furthermore, preventive measures oen fail to reach the major-

ity of people and particularly those most in need and hard to reach, e.g.

with low level of school. Electronic interventions may help to eciently

address multiple HRBs in health care patients. e aim is to introduce the

Proactive Automatized Lifestyle intervention for cancer prevention (PAL)

and to report on how well general hospital patients are reached.

Methods: As part of a study funded by Deutsche Krebshilfe (70113382),

over two months (05-07/2022), all 18- to 64-year old patients admitted to

internal medicine, general surgery, trauma surgery and ear-nose-throat

medicine wards of the University Medicine Hospital Greifswald are sys-

tematically approached and invited to participate in a pre-post-interven-

tion study, irrespective of reason for admission and HRB prole. Based

on psychological behavior change theory, participants (n=175) receive

individualized computer-generated feedback aer baseline and 1 and

3 months later. Reach will be determined by the proportion of partici-

pants among eligible patients. Dierences in reach will be measured with

regards to school education.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts44

Result: To ensure individualization of feedback, a pool of >4000 text

segments, graphics and selection rules has been developed or modied

from previous single behavior interventions. Findings on reach will be

presented.

Discussion: is study is the rst to investigate the reach of a proactive,

electronic and brief multiple behavior change intervention among general

hospital patients.

Conclusions: If reach is high and ecacy established by a randomized

controlled trial, such interventions have potential for the primary and sec-

ondary prevention of cancer diseases.

Disclosure Statement: e authors declare no conict of interest.

Central Nervous System Tumors

Poster

Identication of senolytic agents for sequential treatment of

glioblastoma with temozolomide

Lea Beltzig; Björn Stratenwerth; Markus Christmann; Bernd Kaina

Institute for Toxicology, University Medical Center, Mainz, Deutschland

First-line therapeutic for brain cancer, glioblastoma multiforme (GBM),

is the DNA methylating drug temozolomide (TMZ). It was shown that

TMZ induces autophagy, apoptosis, low level of necroptosis and cellular

senescence (CSEN). We proposed the hypothesis that CSEN is irreversible

and GBM cells may escape from CSEN, giving rise to recurrent tumors.

erefore, treatments that specically target senescent cells, i.e. senolytic

drugs, may lead to a better outome of GBM therapy, by preventing recur-

rences. Here, we tested three natural substances, artesunate, curcumin and

setin, ionising radiation (IR) and, as positive control, a well-known seno-

lytic drug (ABT-737) for their senolytic capacity in GBM cells. Also, sev-

eral proteins involved in the DNA damage response (DDR), ATM, ATR,

pChk1/2, p53, p21, Nf-κB, Rad51, PARP, IAPs and autophagy, a pathway

involved in CSEN induction, were tested for their importance in maintain-

ing CSEN. Treatment of GBM cells with 50 µM TMZ and post-incubated

for 8 days resulted in ~80% CSEN and ~20 % apoptosis, indicatig CSEN

is the major trait induced by TMZ. To identify senolytics, we treated the

senescent population with the compounds of interest and measured the

eect on proliferating and senescent cells. e substances and IR were

used in doses non-toxic on proliferating cells. We show that artesunate,

chloroquine and setine exhibit senolytic activity, killing senescent cells

more eciently than proliferating cells. Curcumin showed the opposite

eect. Although inhibition of ATM, ATR and p53 via pithin-α led to a

decrease in CSEN, indicating their involvement in maintananing CSEN,

no increase in cell death was observed. Obviously, the corresponding inhi-

bitiors do not have senolytic activity. No eect on CSEN was observed by

inhibition of Chk1/Chk2, p21, NF-κB, Rad51, PARP and p53 by pithinµ.

We conclude that these DDR players (except p53) neither play a critical

role in maintaining TMZ-induced CSEN nor can their inhibitors be con-

sidered as senolytics. Since IR did not reduce CSEN, radiotherapy is not

designed to reduce the senescence level.

Disclosure Statement: e authors declare no conict of interest.

Cytotoxic and Senolytic Eects of Methadone in Combination

with Temozolomide in Glioblastoma Cells

Bernd Kaina1; Lea Beltzig1; Andrea Piee-Staa1; Bodo Haas2

1Institute for Toxicology, University Medical Center, Mainz, Deutschland,

2Federal Institute for Drugs and Medical Devices, Bonn, Deutschland

Methadone (MTD), an analgesic drug used for heroin substitution and

pain management, has recently been proposed to be benecial in can-

cer therapy. In vitro Experiments on the most common and severe brain

tumour, glioblastoma multiforme (GBM), treated with doxorubicin and

MTD showed promising results. Since, doxorubicin is not the rst line

treatment for GBM, we sought to determine the eects of the combinato-

rial treatment of MTD with the rst line treatment of GBM, temozolomide

(TMZ). erefore, a human GBM and a human broblast cell line (LN229

and VH10T) were treated with MTD and TMZ alone or in combination,

and induction of cell death and senescence, measured by annexin-V/PI

and c12FDG staining, respectively, were compared. Also, the senolytic

capacity of MTD was analysed. erefore, senescence in MTD treated and

untreated senescent cell was compared.

Treatment of LN229 and VH10T with MTD induced signicant lev-

els of apoptosis und necrosis, starting at a concentration of 20 µg/ml.

Pre-treatment of the cells with Naloxone, a competitive opioid receptor

(OR) inhibitor, did not attenuate this eect, showing its independency of

the opioid receptor. Concurrent treatment of TMZ and non-toxic con-

centration of MTD had no impact on MTD or TMZ-induced cell death.

However, an additive eect of the combinatorial treatment of TMZ with

toxic concentration of MTD (20 µg/ml) was observed. Comet and yH2AX

assays revealed that MTD is not a genotoxic agent. MTD did not induce

senescence, nor did it inuence TMZ induced senescence and despite its

cytotoxic eect on senescent cells, it cannot be considered a senolytic drug

since cytotoxicity was not exclusive to senescent cells.

In conclusion, our data revealed that MTD is cytotoxic on GBM

cell lines in concentrations above the levels reached in vivo. No syner-

gistic eect on cell death or senescence induction by concomitant TMZ

and MTD treatment was observed. Additionally, MTD has no senolytic

capacity. Although a benecial eect of MTD with doxorubicin has been

reported, our data suggest that MTD treatment does not support TMZ

based GBM therapy.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 45

Molecular dosimetry of temozolomide: Quantication of

critical lesions, correlation to cell death responses and

threshold doses

Björn Stratenwerth1; Susanne Geisen2; Yang He1; Lea Beltzig1;

Shana Sturla2; Bernd Kaina1

1Institute for Toxicology, University Medical Center, Mainz, Deutschland

2Department of Health Sciences and Technology, ETH Zürich, Zürich, Schweiz

Temozolomide (TMZ), the rst line treatment for glioblastoma multi-

forme (GBM), induces several alkylating adducts at N- and O-sites of the

DNA, including O6methylguanine (O6MeG). Despite being a minor lesion,

accounting for only 7 % of adducts induced by TMZ, O6MeG is responsible

for almost all genotoxic, cytotoxic, and cytostatic eects caused by TMZ.

O6MeG is repaired by the suicide enzyme MGMT. However, about 40 % of

GBM lack MGMT due to silencing of the gene by promoter methylation.

If not repaired by MGMT, O6MeG lesions provoke futile miss-match-re-

pair cycles resulting nally in DNA double strand breaks (DSBs) in can-

cer cells. How many O6MeG adducts are required to induce specic cell

responses is unknown. erefore, we aimed at determining the dose-de-

pendent formation of O6MeG and set it in relation to DSBs, p53Ser15

phosphorylation, apoptosis/necrosis and cellular senescence. Our results

indicate a linear increase of O6MeG, along with DSBs and p53Ser15 phos-

phorylation. Apoptosis/necrosis and senescence also increased linearly,

with senescence being the main response induced. A possible threshold

for the induction of apoptosis in A172 was indicated by the Hockey-stick

model at a concentration of 2.5 µM TMZ, while no threshold was detected

in LN229 cells. No threshold was detected for senescence. For A172 cells,

treatment with 20 µM TMZ induced 14.000 O6MeG adducts and 32 DSBs,

measured as yH2AX foci, leading to 12 % cell death and 35 % senescence.

Whereas in LN229 cells, 20 µM of TMZ induced 20.600 O6MeG adducts,

66 DSBs, 24 % cell death and 52 % senescence. is data translated to

the therapeutic situation indicate that intra-tumoral concentrations of

TMZ very likely trigger a signicant amount of cytotoxic and cytostatic

cell responses. is notion is further supported by an accumulation of

cytotoxic responses in a low dose repeated treatment protocol. e low

benecial properties of TMZ might result from the low rate of cell death

compared to senescence. Since TMZ/O6MeG responses require prolifer-

ation, senescent cells inevitably escape the cytotoxic eects of the drug.

Disclosure Statement: e authors declare no conict of interest.

140

Human bone marrow-derived mesenchymal stromal cells

increase glioblastoma radioresistance

Maren Strack1,2; Alexander Rühle1,2; Dieter Henrik Heiland3; Oliver Schnell3;

Anca-L. Grosu1,2; Nils Henrik Nicolay1,2

1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im

Breisgau, Deutschland,

2Deutsches Konsortium für Translationale Krebsforschung (DKTK),

Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Deutschland,

3Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Freiburg im Breisgau,

Deutschland

Background: Previous studies have shown that the number of tumor-in-

ltrating mesenchymal stromal cells (MSCs) inversely correlates with the

survival of glioblastoma (GBM) patients, providing a rationale to examine

whether MSCs causally contribute to the poor radiation response of glio-

blastoma cells (GBCs).

Methods: e immortalized cell line U251 and two primary GBCs, iso-

lated from surgical samples of a primary and a recurrent GBM, were

co-cultured with human bone-marrow derived MSCs from three dier-

ent donors. Colony forming, proliferation and metabolic viability assays

were performed to analyze the inuence of MSCs on the radiosensitivity

of GBCs. A modied Boyden Chamber migration assay was used to

examine the eect of radiotherapy on GBCs’ ability to attract MSCs

chemotactically.

Cell cycle distribution and apoptosis rates were quantied by ow

cytometry, while the expression of the radioresistance-related Growth

Associated Protein 43 (GAP43) was studied based on immunuorescene

stainings.

Result: Direct MSC co-culture increased GSCs’ clonogenic survival and

proliferation aer irradiation, whereas MSC-conditioned medium did not

aect GBCs’ metabolic activity. e number of MSCs migrating towards

primary GBCs decreased aer irradiation of GBCs, suggesting reduced

release of chemotactic factors by GBCs. Presence of MSCs caused a pro-

nounced G2/M phase arrest and reduced apoptosis rates in primary GBCs

aer irradiation. GAP43 expression in GBCs was considerably enhanced

when co-cultured with MSCs.

Discussion: Bone marrow-derived MSCs exert radioprotective eects

on GBCs which could partly explain the pro-tumorigenic eect of

tumor-inltrating MSCs in glioblastoma patients. As co-culturing with

MSCs increases the expression of GAP43 in GBCs, we established an siR-

NA-based knockdown to analyze whether GAP43 silencing can mitigate

MSCs’ radioprotective eects.

Conclusion: Bone-marrow derived MSCs increase the radioresistance of

GBCs in vitro.

Disclosure Statement: e authors declare no conict of interest.

254

Quality of life of patients with newly diagnosed glioblastoma

during TTFields therapy in routine clinical care: rst results of

the TIGER study

Oliver Bähr1; Ghazaleh Tabatabai2; Rainer Fietkau3; Roland Goldbrunner4;

Martin Glas5,6

1General Hospital Aschaenburg-Alzenau, Department of Neurology,

Aschaenburg, Deutschland

2University Hospital Tuebingen, Department of Neurology and Interdisciplinary

Neurooncology, Tübingen, Deutschland

3University Hospital Erlangen, Department of Radiation Oncology, Erlangen,

Deutschland

4University Hospital Cologne, Center for Neurosurgery, Köln, Deutschland

5University Hospital Essen, University Duisburg-Essen, Division of Clinical

Neurooncology, Department of Neurology, Essen, Deutschland

6University Hospital Essen, University Duisburg-Essen, West German Cancer

Center (WTZ) and German Cancer Consortium Partner Site, Essen, Deutschland

Background: Glioblastoma (GBM) is an aggressive primary tumor of the

central nervous system. Current treatment strategies include maximal safe

resection, followed by treatment with radiation and an alkylating chemo-

therapy. Based on the positive phase 3 trial EF-14, the addition of Tumor

Treating Fields (TTFields) to temozolomide (TMZ) maintenance therapy

brought an additional treatment method to clinical routine. e TIGER

(TTFields In GErmany in Routine Clinical Care) study documents the use

of TTFields in routine clinical care focusing on health-related quality of

life (HRQoL), treatment compliance and duration.

Methods: is multi-center prospective non-interventional study in

Germany (NCT03258021) included ndGBM patients eligible for TTFields

therapy. Following their consent to participate in the study, patients

received a comprehensive introduction to the therapy and their baseline

(BL) demographic data were collected. Information on TTFields ther-

apy decision is evaluated based on a dedicated TTFields questionnaire at

BL in both arms, follow-up information on how patients cope with the

therapy is collected 2 months aer TTFields treatment start, if applicable.

HRQoL was assessed in patients deciding for TTFields therapy at BL as

well as at 2 and 4 months thereaer using the EORTC-QLQ-C30/BN-20

questionnaires.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts46

Result: Between August 2017 and November 2019, 710 patients (259

female/451 male) were enrolled at 81 centers. e mean age was 58.5

years (range: 19.0-85.0). e overall BL characteristics of the study group

reects a typical GBM population. 582 (82%) decided to start TTFields

and 128 (18%) refused TTFields treatment. HRQoL did not decline

during TTFields therapy except for itchy skin, comparable to the results

of the EF-14 phase 3 trial. A detailed analysis of the cohort as well as their

reported QoL will be presented.

Conclusion: e TIGER study is the largest non-interventional trial on

the use of TTFields in routine clinical care. e use of TTFields in patients

with ndGBM did not impair HRQoL during the follow-up period, except

for more itchy skin.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

275

Intracranial metastases from prostate cancer - Retrospective

analysis of a clinical cohort study

Fortesa Bytyqi; Sebastian Thomas; Cornelia Cedzich; Jan Walter

Klinikum Saarbrücken , Neurochirurgie, Saarbrücken, Deutschland

Objective: Cerebral metastases arising from prostate cancer have been

described in literature rarely and poorly. e aim of this study is to pres-

ent the epidemiology, diagnostic regime, clinical presentation, therapeutic

strategies and prognosis of intracranial metastatic prostate cancer patients.

Methods: Single center retrospective meta-analysis of a clinical cohort

study including patients with prostate cancer that have been hospitalized

between 2008 and 2018. Clinical presentation was classied using the

National Institutes of Health Stroke Scale (NIHSS) and outcome was mea-

sured by the modied Rankin Scale (mRS).

Results: Out of 2450 patients with prostate cancer, 8 cases with intracra-

nial metastases were identied. In three patients the diagnosis could be

veried histologically. e cumulative incidence was 0.33 %. e median

age of patients with intracranial prostate cancer metastases was 69.8 years

(range: 62 – 74). e average time interval from the diagnosis of prostate

cancer until detection of brain metastases was 5.7 years (range 1 – 15). In

the three surgical cases resection of the brain metastases led to a signif-

icant improvement of neurological symptoms (NIHSS) and outcome at

discharge (mRS). All three operated metastases were adenocarcinomas of

the prostate.

Conclusion: e presented results are in line with those of previous inter-

national multicenter studies. Brain metastases due to prostate cancer are

rare. Nevertheless, in cases of new neurological decits in patients with

prostate cancer, a cerebral dissemination of the primary tumor has to be

considered in the dierential diagnoses. Considering general prognosis

in the setting of an intracranially metastasized prostate cancer further

studies with larger case numbers and more detailed specications of the

primary tumor are recommended.

Disclosure Statement: e authors declare no conict of interest.

404

Molecular analyses of Glioblastoma patient-derived xenograft

(PDX) models identify potential targets in treatment resistant

tumors

Joshua Alcaniz1; Mathias Dahlmann1; Theresia Conrad1;

Andrea Orthmann1; Johannes Haybaeck2,3,4; Stefanie Krassnig2;

Christina Wodlej3; Anna Maria Birkl-Toeglhofer2,4; Tobias Kratzsch5;

Susanne Antje Kuhn6; Andreas Joedicke7; Fichtner Iduna1,8;

Jens Homann1; Wolfgang Walther1,9

1EPO Berlin-Buch GmbH, Berlin, Deutschland

2Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology,

Medical University of Graz, Graz, Österreich

3Center for Biomarker Research in Medicine, Graz, Österreich

4Institute of Pathology, Neuropathology and Molecular Pathology, Medical

University of Innsbruck, Innsbruck, Österreich

5Department of Neurosurgery, Charité University Hospital, Berlin, Deutschland

6Department of Neurosurgery, Ernst von Bergmann Hospital, Potsdam,

Deutschland

7Department of Neurosurgery, Vivantes Hospital Berlin Neukölln, Berlin,

Deutschland

8Max Delbrueck Center for Molecular Medicine, Berlin, Deutschland

9Experimental and Clinical Research Center , Charité, Universitätsmedizin Berlin,

Translational Oncology, Berlin, Deutschland

Background: Glioblastoma (GBM) is the most common malignant

brain intrinsic tumor in adults, with about 90% of tumors developing de

novo. eir heterogeneity and aggressive, inltrative growth limit suc-

cess of current standard of care and ecacy of various new therapeutic

approaches. To analyze the molecular mechanisms of tumorigenesis and

resistance to therapy, as well as to identify new therapeutic targets, mod-

els reecting the complex biology of these tumors are urgently needed.

erefore patient-derived xenogra (PDX) models are an essential tool

in GBM research.

Methods: We established a panel of 27 PDX glioma models on immu-

nodecient mice (6 of these by othotopic transplantation). Sensitivity

towards a panel of drugs, selected on their modes of action or ability to

pass the blood-brain-barrier (BBB) was determined. Currently, 19 models

have been analyzed for mutations and gene expression proles using panel

and transcriptome sequencing.

Results: Best treatment responses (growth inhibition > 50%) were

observed for SoC Temozolomide (TMZ), Irinotecan and Bevacizumab.

Molecular characterization allowed the identication of frequent muta-

tions - i.e. in the genes KDR, FGFR3, PIK3CA, PTEN and P53 - and

expression signatures, like the activation of upstream regulators HDAC1/2

and ATM in TMZ resistant models. Identied potential new predictive

markers and targets are currently being analyzed.

Discussion: Our sensitivity screens identied irinotecan or bevacizumab

as treatment alternatives in most TMZ resistant PDX models. For their

benecial use in GBM treatment however, there is still need for predictive

markers.

Conclusion: e established PDX panel is a valuable tool to validate

these, as well as to identify new possible targets and assess new treatment

approaches.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 47

460

Tumor Treating Fields reduce the survival and migration

potential of human mesenchymal stromal cells

Alexander Rühle1,2; Maren Strack1,2; Yaara Porat3; Moshe Giladi3;

Anca-L. Grosu1,2; Nils Henrik Nicolay1,2

1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im

Breisgau, Deutschland

2Deutsches Konsortium für Translationale Krebsforschung (DKTK),

Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Deutschland

3Novocure Ltd., Haifa, Israel

Background: Tumor Treating Fields (TTFields) have shown clinical e-

cacy in glioblastoma treatment. As mesenchymal stromal cells (MSCs)

belong to the glioblastoma microenvironment and impair the prognosis

of glioblastoma patients, we studied the eects of TTFields on the sur-

vival, migration potential and stem cell characteristics of MSCs.

Methods: Human MSCs were harvested from the bone marrow of three

donors and treated with TTFields for 72h using the inovitro™ system.

Clonogenic survival, proliferation and resazurin assays were conducted

with dierent TTFields frequencies and eld intensities. TTFields-

induced senescence was quantied with β-galactosidase stainings, and

ow cytometry analyses were performed to analyze MSCs’ characteristic

surface marker expression and apoptosis rates. Boyden chamber assays

were carried out to measure the inuence of TTFields on MSCs’ migration

potential.

Result: TTFields reduced cellular proliferation of all analyzed MSC sam-

ples by 45-60% compared to untreated controls, whereas MSCs’ clono-

genic survival was reduced by 73–88%. In contrast, metabolic viability

of MSCs was largely unaected aer TTFields. e anti-proliferative

eect of TTFields on MSCs was relatively independent of the alternat-

ing current’s frequency within a range of 100-500 kHz. TTFields resulted

in signicantly increased senescence and apoptosis rates, as detected by

increased caspase-3 and annexin-V levels, while the characteristic MSC-

surface marker expression was found intact. TTFields led to a signicantly

impaired migratory potential of MSCs.

Discussion: MSCs are able to migrate to glioblastoma cells and exert

pleiotropic pro-tumorigenic eects (e.g., neo-angiogenesis, immunosup-

pression, resistance to radiotherapy). e observed sensitivity of MSCs

towards TTFields may therefore contribute to the anti-glioblastoma

eects of TTFields.

Conclusion: Human MSCs exhibit a TTFields-sensitive phenotype, pro-

viding a rationale to target tumor-associated MSCs as part of the glioblas-

toma microenvironment using TTFields.

Disclosure Statement: e authors declare the following:

e project received research funding by Novocure Ltd., and Yaara Porat and

Moshe Giladi are paid full-time employees of Novocure. Alexander Rühle served

as consultant for Novocure Ltd.

465

Bcl6- a potential marker of prognosis in glioblastoma patients

Hannes Treiber1; Christian von der Brelie2; Judith Büntzel1

1Georg-August-Universität, Universitätsmedizin Göttingen, Klinik für

Hämatologie und Onkologie, Göttingen, Deutschland

2Georg-August-Universität, Universitätsmedizin Göttingen, Klinik für

Neurochirurgie, Göttingen, Deutschland

Background: Response to treatment aer surgery and radiation ther-

apy is evaluated by MRI scan in glioblastoma patients. However, MRI

scan does not always dierentiate between early progression and pseu-

do-progression. A discriminating biomarker does not exist. B-cell lym-

phoma 6 (BCL6) plays a central role in lymphocyte maturation and

lymphomagenesis, but was recently found upregulated in glioblastoma

tissue. Wehypothesized that bcl6 may serve as a biomarker accessible via

extracellular vesicles of cancer cells which are secreted into the peripheral

blood.

Methods: Small extracellular vesicles (sEV) were extracted from the

peripheral blood of 37 glioblastoma patients by dierential centrifugation.

Western blotting was used to assess BCL6 content of sEV. BCL6 status of

patients were either rated as “positive” or “negative”. BCL6 status was cor-

related with overall survival using Kaplan-Meier curves.

Result: BCL6 was observed in the sEV of a sub-cohort of 22 glioblastoma

patients. is group showed an overall survival (OS) of 15.6 months,

whereas BCL6-negative patients had an OS of 35.6 months (p = 0.016). All

patients with recurrent disease (N=6) were positive for BCL6 expression

in sEV. All BCL6-negative patients were recruited during stable disease or

at the time of primary diagnosis.

Discussion: We demonstrate presence of BCL6 protein in sEVs. Detection

of BCL6 in sEV was correlated with worse prognosis in glioblastoma

patients and may represent clonal evolution during the disease. Assessing

BCL6 status may have prognostic implications and help to dierentiate

between progression and pseudo-progression. However, a prospective

trial with a larger cohort is required to validate the value of BCL6 as a

biomarker in glioblastoma.

Conclusion: BCL6 has the potential to become a marker for progressive

disease and worse prognosis in glioblastoma patients.

Disclosure Statement: e authors declare no conict of interest.

474

Pseudomyogenic hemangioendothelioma with ACTB-FOSB

gene fusion: case report of intracerebral metastases

Anja Glien1; Lhagva Sanchin1; Dirk Vordermark2; Timo Behlendorf3;

Hans-Jörg Meisel1; Christian Mawrin4

1Klinik für Neurochirurgie, BG Klinikum Bergmannstrost Halle, Halle,

Deutschland

2Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle,

Halle, Deutschland

3Onkologische Gemeinschaftspraxis, Halle, Deutschland

4Institut für Neuropathologie, Otto-von-Guericke Universität, Magdeburg,

Deutschland

Background: Pseudomyogenic hemangioendothelioma (PMH) is a rare

vascular tumor, oen occuring multifocal, predominantly involving

the trunk or extremities and aecting men of younger age. Described

as a tumor entity of indolent behavior, it was classied in the WHO

Classication of tumors of so tissue and bone in 2013 with low met-

astatic potential. Typically PMH tumors are resected, but two-thirds of

cases show multifocal lesions, oen involving dierent types of tissue

simultaneously. Metastases are almost uncommon, distant metastases

presenting at initial diagnosis seem to be extremely rare. Resection is oen

dicult, moreover a signicant risk of local recurrence is described. To

date, in case of unresectable tumor lesions eective therapeutic strategies

have not been established. In some cases radiotherapy is applied, while

chemotherapy mostly seems to be ineective. However, mTOR inhibitors

showed promising results of disease stabilization.

Methods: Herein, we present a case of a 59-year-old male with multi-

ple intracerebral metastases of a PMH who was treated with stereotactic

radiotherapy, followed by systemic therapy.

Result: Histopathologic examination revealed a pseudomyogenic heman-

gioendothelioma. Molecular analysis identied a ACTB-FOSB gene

fusion, and immunohistochemistry showed expression of somatostatin

receptors in the tumor tissue.

Conclusion: PMH with distant metastases occurring in the central ner-

vous system is extremely rare and needs identication of systemic treat-

ment options.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts48

758

Dexamethasone blunts the ecacy of locally administered

immunostimulatory gene therapy in murine glioblastoma

Marilin Koch1,2; Mykola Zdioruk1; Michael Nowicki1; Alec Grith3;

Estuardo Aguilar-Cordova4; Laura Aguilar4; Francesca Barone4;

Brian W Guzik4; Paul Peter Tak4; Ghazaleh Tabatabai2; James Lederer3;

E. Antonio Chiocca1; Sean Lawler1

1Harvey Cushing Neurooncology Laboratories, Department of Neurosurgery,

Brigham & Women’s Hospital, Harvard Medical School, Boston, USA

2Department of Neurology and Interdisciplinary Neuro-Oncology, Hertie

Institute for Clinical Brain Research, Eberhard Karls University Tübingen,

Tübingen, Deutschland

3Department of Surgery, Brigham & Women’s Hospital, Harvard Medical School,

Boston, USA

4Candel Therapeutics, Needham, USA

Background: Local immunostimulatory therapies are a promising

approach in the treatment of glioblastoma. e corticosteroid, dexa-

methasone, is frequently required to alleviate edema in this disease

and may compromise the ecacy of immunotherapies. CAN-2409 is a

locally administered immunotherapy that uses aglatimagene besadenovec

(AdV-tk) with an anti-herpetic prodrug to induce tumor cell death by

attracting immune cells to the tumor site. How combined dexamethasone

inuences ecacy of this and other local immunotherapies are unknown

Methods: We investigated the impact of dexamethasone on CAN-2409 in

vitro by cell viability and T-cell mediated tumor killing assays and in vivo

using an orthotopic syngeneic glioblastoma mouse model. Alterations of

the tumor microenvironment in experimental groups were assessed by

mass cytometry (CyTOF) analyses.

Result: In vitro assays showed that dexamethasone signicantly impaired

CAN-2409 mediated anti-tumor cytotoxicity and immunogenicity. In vivo,

we observed a signicant reduction in median survival (29d) of CAN-

2409 and dexamethasone combined treatment as compared to CAN-2409

alone (39.5d) (p= 0.018). CyTOF analyses demonstrated an increase in

macrophage and neutrophil populations and a decrease in T-cells and

B-cells in mice treated with dexamethasone and CAN-2409. Tumor inl-

trating immune cells from mice treated with dexamethasone expressed

higher immune cell exhaustion and pro-tumorigenic cell markers.

Discussion: Our data suggest that dexamethasone may reduce the ecacy

of locally delivered immunotherapies in glioblastoma.

Conclusion: ese results support the idea that dexamethasone use

should be avoided or limited to the lowest necessary dose.

Disclosure Statement: e authors declare no conict of interest.

768

Targeting c-IAP1, c-IAP2, and Bcl-2 eliminates senescent

glioblastoma cells following temozolomide treatment

Christian Schwarzenbach; Larissa Tatsch; Juliana Brandstetter Vilar;

Birgit Rasenberger; Lea Beltzig; Bernd Kaina; Maja Tomicic;

Markus Christmann

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Institut für

Toxikologie, Mainz, Deutschland

Background: Glioblastoma multiforme is the most aggressive, highly

recurring form of diuse brain tumours and rst-line therapy is composed

of resection followed by ionizing radiation and adjuvant TMZ dosage. In

previous work, we showed that TMZ induces mostly senescence and not

cell death, which is associated with a G2-phase arrest and an increase in

polyploidy. We aimed to identify senolytic drugs to increase the ecacy of

glioblastoma treatment and reduce its burden on the patient.

Methods: erefore, cell death, senescence, cell cycle progression

were analysed by ow cytometry and the expression of senescent cell

anti-apoptotic factors (SCAFs) was analysed by qPCR and immunodetec-

tion in LN229, U87 and A172 glioblastoma cells upon exposure to TMZ.

Furthermore, we evaluated the impact of these potential SCAFs on cell

death by making use of the small molecule inhibitors embelin (targets

XIAP), AT406 (targets c-IAP1 > XIAP), BV6 (targets c-IAP1, c-IAP2

and marginal XIAP) and Venetoclax (targets Bcl-2) and performed

COMBENEFIT analysis for synergy.

Result: SCAFs Bcl-2, Bcl-XL and c-IAP1, c-IAP2 showed strong

expression. Exposure of TMZ-induced senescent cells to non-toxic

concentrations of the inhibitors showed that BV6 and Venetoclax sig-

nicantly induced subG1- and AnnexinV/PI- positive cells, alone and in

combination.

Conclusion: We conclude that the upregulation of the antiapoptotic fac-

tors c-IAP1, c-IAP2 and Bcl-2 during TMZ-induced senescence is a key

event in the protection from cell death, and inhibition of these factors

eectively kills senescent glioblastoma cells.

Indication of source:

1 Schwarzenbach, C.; Tatsch, L.; Brandstetter Vilar, J.; Rasenberger, B.; Beltzig, L.;

Kaina, B.; Tomicic, M.T.; Christmann, M. Targeting c-IAP1, c-IAP2, and Bcl-2

Eliminates Senescent Glioblastoma Cells Following Temozolomide Treatment.

Cancers 2021, 13, 3585.

Disclosure Statement: e authors declare no conict of interest.

847

The Role of Stereotactic Radiosurgery in the Management

of Foramen Magnum Meningiomas — A Multicenter Analysis

Felix Ehret1; Markus Kufeld2; Christoph Fürweger2; Alfred Haidenberger2;

Susanne Fichte3; Ralph Lehrke4; Carolin Senger1; David Kaul1; Martin Bleif5;

Gerd Becker5; Daniel Rueß6; Maximilian Ruge6; Christian Schichor7;

Jörg-Christian Tonn7; Alexander Muacevic2

1Charité - Universitätsmedizin Berlin, Berlin, Deutschland

2Europäisches Radiochirurgie Centrum, München, Deutschland

3CyberKnife Zentrum Mitteldeutschland, Erfurt, Deutschland

4Deutsches CyberKnife Zentrum, Westfalen, Deutschland

5RadioChirurgicum, Göppingen, Deutschland

6Universitätsklinik Köln, Köln, Deutschland

7Ludwig-Maximilians-Universität München, München, Deutschland

Background: Foramen magnum meningiomas (FMMs) represent a

considerable neurosurgical challenge given their location and potential

morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive

treatment modality for various brain tumors. However, reports on SRS

or fractionated stereotactic radiotherapy for the management of FMMs

are rare. Herein, we report our multicenter treatment experience utilizing

robotic radiosurgery.

Methods: Patients who underwent SRS between 2005 and 2020 as a treat-

ment for FMMs at six dierent centers were eligible for analysis. All treat-

ments were delivered using the CyberKnife robotic radiosurgery system

(Accuray Inc., Sunnyvale, CA, USA). Local tumor control (LC), symp-

toms, and adverse events were evaluated clinically and radiographically.

Result: Sixty-two patients were included. e median follow-up was 28.9

months. e median prescription dose and isodose line were 14 Gy and

70%, respectively. Single-fraction SRS accounted for 81% of treatments.

Ten patients were treated for a tumor recurrence aer surgery, and thir-

teen underwent adjuvant treatment. e remaining 39 FMMs received

SRS as their primary treatment. e median tumor volume was 2.6 cubic

centimeters. No local failures were observed, leading to an overall LC of

100%. Tumor volume signicantly decreased aer treatment (p < 0.01).

Most patients showed stable (47%) or improved (21%) neurological de-

cits at the last follow-up. No high-grade adverse events were observed.

Discussion: SRS treatment results for FMMs were favorable and in agree-

ment with the available literature. No signicant toxicity was observed.

Given the potential implications of surgical resection, SRS can be a viable

treatment alternative in patients, especially in those with subtotal tumor

resections, recurrences, and patients not suitable for surgery.

Conclusion: SRS is an eective and safe treatment modality for FMMs.

Despite the paucity of available data, SRS should be considered for

selected patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 49

943

First clinical experience on fractionated intracavitary

radioimmunotherapy with Lu-177 labeled 6A10 Fab

fragments in glioblastoma

Michael Müther1; Wolfgang Roll2; Guido Böning3; Astrid Delker4;

Franz-Josef Gildehaus4; Michael Schäfers2; Reinhard Zeidler5;

Hans-Jürgen Reulen6; Lars Stegger2; Walter Stummer1

1Münster, Universitätsklinikum Münster, Klinik für Neurochirurgie, Münster,

Deutschland

2Münster, Universitätsklinikum Münster, Klinik für Nuklearmedizin, Münster,

Deutschland

3Universität München, Klinikum Großhadern, Klinik für Nuklearmedizin,

München, Deutschland

4Universität München, Klinikum Großhadern, Klinik für Nuklearmedizin,

München, Deutschland

5Helmholtz Zentrum München, München, Deutschland

6Universität München, Klinikum Großhadern, Klinik für Neurochirurgie,

München, Deutschland

Background: Maintenance therapies for glioblastoma are lacking.

Adjuvant radio-immunotherapy (RIT) with Lu-177 labeled 6A10-Fab

fragments, targeting tumor-associated carbonic anhydrase XII (CA12),

applied into the resection cavity, oers a promising strategy to address

hibernating tumor burden. We report on the rst in human applications.

Methods: ree patients underwent microsurgical resection of glioblas-

toma. Aer completion of standard adjuvant radio- and chemotherapy,

RIT was oered as compassionate use. Aer implantation of an injection

reservoir into the tumor cavity, the protocol included three consecutive

doses of Lu-177 labeled 6A10 Fab fragments over three months, cor-

responding to 25% - 50% - 25% of the total activity. Injected dose was

adapted to the size of the resection cavity. Dosimetry was performed with

planar whole-body scintigraphy and SPECT/CT 12h, 24h, 48h, 76h and

5-7 days aer injection.

Result: Patient #1 (IDH1-Mutation) received three doses of RIT (592

MBq) with stable disease 12 months aer therapy and 26 months aer ini-

tial diagnosis. Patient (IDH-Wildtype) #2 had histologically proven tumor

progression aer the second cycle (526 MBq). Patient #3 (IDH-Wildtype)

has so far received the one cycle (administered 327 MBq, planned total

1300 MBq). No toxicity according to CTCAE version 6.0 or other adverse

events related to RIT were observed. Dosimetry did not reveal absorbed

doses above the upper dose limit for organs at risk. In the rst two patients,

the calculated absorbed kidney dose was approximately 3.0 +- 1.0 mGy/

MBq and the hematopoietic bone marrow was 0.04 +- 0.01 mGy/MBq.

Discussion: Intracavitary radioimmunotherapy with Lu-177 labeled

6A10-Fab fragments appears to be a safe maintenance therapy for glio-

blastoma patients, albeit only assessed in three compassionate use situ-

ations far.

Conclusion: A multicenter conrmatory phase-I-trial will be initiated in

May 2022 (EudraCT-No: 2015-004417-25) to determine the maximum

tolerated dose and safety of adjuvant RIT with Lu-177 labeled 6A10-Fab

fragments.

Disclosure Statement: e authors declare no conict of interest.

Developmental Therapeutics: Immunotherapy/Cellular

Best-of-Abstract-Vortrag

208

Idecabtagene vicleucel (ide-cel, bb2121) in Relapsed

and Refractory Multiple Myeloma (RRMM): Analyses of

High-Risk Subgroups in the KarMMa Study

Hartmut Goldschmidt1; Noopur Raje2; David Siegel3; Sundar Jagannath4;

Sagar Lonial5; Nikhil Munshi6; Philippe Moreau7; Michele Cavo8;

Anna Truppel-Hartmann9; Everton Rowe10; Liping Huang10;

Amit Agarwal10; Julie Wang10; Timothy Campbell10; Jesus San-Miguel11;

Donna Reece12

1University Hospital Heidelberg and National Center for Tumor Diseases,

Heidelberg, Deutschland

2Massachusetts General Hospital, Boston, USA

3Hackensack University Medical Center, Hackensack, USA

4Mount Sinai Hospital, New York, USA

5Emory School of Medicine, Atlanta, USA

6Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma

Therapeutic, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA

7Centre Hospitalier Universitaire de Nantes, Nantes, Frankreich

8Seràgnoli Institute of Hematology, Bologna University School of Medicine,

Bologna, Italien

9bluebird bio, Cambridge, USA

10Bristol Myers Squibb, Princeton, USA

11Clinica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Navarra, Spanien

12Princess Margaret Cancer Centre, Toronto, Kanada

Background:Patients (pts) with high-risk RRMM receiving conventional

care face poor outcomes. Ide-cel, a BCMA-directed CAR T cell therapy

(tx), demonstrated frequent, deep and durable responses in RRMM pts in

the pivotal phase 2 KarMMa study (NCT03361748).1 We report updated

safety and ecacy results for ide-cel in high-risk subgroups from the

KarMMa study.

Methods:Pts had ≥3 prior lines of tx (immunomodulatory agent, prote-

asome inhibitor, and anti-CD38 antibody inclusive) and were refractory

to their last regimen. Aer lymphodepletion, pts received target doses

of 150–450 × 106 CAR+ T cells.1 Subgroup analyses were performed in

pts stratied by extramedullary disease (EMD), high-risk cytogenet-

ics [del(17p), t(4;14), t(14;16)], high tumor burden (≥50% bone mar-

row plasma cells), receipt of bridging tx, baseline disease stage (revised

International Staging System), and >1 prior regimen/year. Primary end-

point was overall response rate (ORR).

Results:Among 128 ide-cel–treated pts, 39% had EMD, 35% had high-

risk cytogenetics, 51% had high tumor burden, 88% received bridging tx,

16% had disease stage III, and 47% received >1 prior regimen/year. At the

cuto date (21 Dec 2020), ORR was ≥65% and complete response rate

was ≥22% across all high-risk subgroups examined except disease stage

III (48% and 10%, respectively). ORR was not substantially aected by

presence of EMD (70% w/ and 76% w/o) or high baseline tumor burden

(71% w/ and 77% w/o). Median duration of response was ≥9.2 mo and

median progression-free survival was ≥6.1 mo in all high-risk subgroups

except disease stage III (6.9 mo and 4.9 mo, respectively). No new safety

signals were identied.

Discussion: Ide-cel continues to demonstrate benet, even in historically

dicult-to-treat pts, including pts with high-risk features such as EMD,

high-risk cytogenetics, high tumor burden, and receipt of bridging tx or

>1 prior regimen/year.

Conclusions: ese results suggest that ide-cel represents a promising

treatment option for pts with high-risk RRMM.

Reference:

1. Munshi NC, et al.N Engl J Med 2021;384:705–716.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts50

Poster

Feasibility of eftilagimod alpha combined with avelumab

in advanced solid tumors: advanced safety and ecacy data

from Stratum D of the phase I INSIGHT platform trial

Thorsten O. Goetze1,2; Daniel W. Mueller1,2; Mohammad-Reza Rayan3;

Dragan Kiselicki3; Timursah Habibzade3; Marina Schaaf2;

DisornSookthai2; Regina Eickho2; Elke Jäger3; Salah-Eddin Al-Batran1,2

1Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt am

Main, Deutschland

2Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest,

Frankfurt am Main, Deutschland

3Krankenhaus Nordwest, Frankfurt, Frankfurt am Main, Deutschland

Background: Stratum D of the INSIGHT platform trial evaluates eilagi-

mod alpha (ei) combined with avelumab in advanced solid tumors. Ei

is an MHC class II agonist which activates antigen-presenting cells fol-

lowed by CD8 T-cell activation. Combination with PD-1/PD-L1 blockade

aims at enhanced ecacy.

Methods: is phase I trial consists of 5 strata: intratumoral (A) or intra-

peritoneal ei (B); s.c. ei with SOC (C) or with PD-L1 inhibition (D).

Strat E is currently under development with a new ei combination. is

abstract focuses on Strat D: 800mg avelumab i.v. q2w along with s.c. ei:

6mg (cohort 1, 6 pts), 30mg (cohort 2, 6 pts). e primary endpoint is

safety.

Result: e trial was completed with 12 pts (cohort [coh] 1: gastric, gall-

bladder, colon, pleural mesothelioma; coh 2: gastric, gastroesophageal,

anal, rectum, cervix uteri). No dose limiting toxicities occurred. 10 serious

adverse events were reported, none of them related to the IMPs (4 SAEs

in 3 pts coh 1 [1 acute renal insuciency grade 5 in 1 pt, 2 preileus grade

3 in 1 pt, 1 hearing impaired grade 4 in 1 pt] and 6 SAEs in 4 pts coh 2

[1 anal hemorrhage and 1 gallbladder obstruction in 1 pt, 1 eye pain and

1 feeding tube dislocation in 1 pt, each grade 3, 1 skin infection grade

2, 1 diuse myocardial brosis grade 5]. 1 AE of special interest (AESI)

related to avelumab (sarcoidosis grade 1) occurred. 2 pts completed max

treatment with 24 cycles. 5 pts showed partial response, 1 stable disease,

5 progressive disease acc. to RECIST 1.1, 1 clinical progression. Activity

was also observed in pre-treated non- immunogenic tumors. In the entire

study population 75% were still alive, 66.7% of coh 1, 83.3% of coh 2.

Discussion: Treatment with avelumab and ei 6mg or 30mg was well tol-

erated with no unexpected AEs. Signals of ecacy targeting the axis of

PD-L1 in combination LAG-3-agonism were seen (disease control rate

of 50%).

Conclusion: 30 mg ei appears to be feasible and safe.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Co-stimulatory bispecic antibodies induce enhanced T cell

activation and tumor cell killing in breast cancer models

Karsten Michael Warwas1,2; Marten Meyer1,2; Márcia Gonçalves1,2;

Annkathrin Teschner1,2; Gerhard Moldenhauer3; Claus Peter Heußel4,5,6;

Inka Zörnig7; Dirk Jäger1,7; Frank Momburg2,7

1German Cancer Research Center (DKFZ), Clinical Cooperation Unit Applied

Tumor Immunity, Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Antigen Presentation and T/NK Cell

Activation Group, Heidelberg, Deutschland

3German Cancer Research Center (DKFZ), Department of Translational

Immunology, Heidelberg, Deutschland

4University Hospital Heidelberg, Thoraxklinik Heidelberg, Diagnostic and

Interventional Radiology with Nuclear Medicine, Heidelberg, Deutschland

5University Hospital Heidelberg, Department of Diagnostic and Interventional

Radiology, Heidelberg, Deutschland

6German Lung Research Center (DZL), Translational Lung Research Center

Heidelberg (TLRC), Heidelberg, Deutschland

7University Hospital Heidelberg, National Center for Tumor Diseases (NCT),

Department of Medical Oncology, Heidelberg, Deutschland

Background: Although T cell-recruiting CD3-binding bispecic anti-

bodies (BiMAb) are clinically eective for hematologic malignancies, the

success of BiMAb targeting solid tumor-associated antigens (TAA) in

carcinomas remains poor. We reasoned that provision of co-stimulatory

BiMAb in combination with αCD3 BiMAb would boost T cell responses,

facilitating targeting of weakly or heterogeneously expressed tumor

antigens.

Methods: We analyzed αTAA–αCD3/αCD28 BiMAb, targeting breast

cancer antigens including HER2, EGFR, CEA, and EpCAM. Moreover,

we tested bifunctional fusion proteins of tumor necrosis factor ligand

(TNFL) superfamily members such as 4-1BBL, OX40L, CD70 and TL1A.

Functional activity was evaluated in cell-based assays. Anti-tumor activity

was conrmed in a patient-derived 3D spheroid model using pleural eu-

sions of breast cancer patients.

Result: Only in presence of tumor cells, αCD3 BiMAb activated T

cells and induced cytotoxicity in vitro, indicating strict dependence on

cross-linking. Combination treatment of αCD3 with αCD28 or TNFL

bispecics drastically enhanced T cell proliferation, activation marker

expression, cytokine secretion and tumor cytotoxicity, reducing the

required dose to achieve T cell activation. Immune checkpoint inhibi-

tors further augmented BiMAb-mediated co-stimulation. In patient-de-

rived spheroids, co-stimulatory BiMAb were essential for activation

of tumor-inltrating lymphocytes and cytotoxic anti-tumor responses

against breast cancercells.

Discussion: Co-stimulatory bispecics signicantly potentiated the

tumoricidal activity of αCD3 BiMAb while preserving dependence on

TAA recognition. When co-stimulation involves a second tumor-associ-

ated antigen or a tumor stromal antigen, such approach could provide for

a more localized activation of the immune system with higher ecacy and

reduced peripheral toxicities.

Conclusion: Combining stimulatory and co-stimulatory BiMAb may

have promising clinical application in the treatment of solid tumors.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 51

Recurrence of hepatocellular carcinoma can be predicted by

PD-1 expression and immune-active lymphocytes

Gabriel Fridolin Hess1,2; Jasmin Zeindler1; Silvio Däster1; Simone Muenst3;

Caner Ercan2,3; Jürg Vosbeck3; Mairene Coto-Llerena2,3;

Salvatore Piscuoglio2,3; Otto Kollmar1; Savas Deniz Soysal1

1Clarunis Viszeralchirurgie, Universitätsspital Basel , Basel, Schweiz

2Departement Biomedizin, Universität Basel und Universitätsspital Basel, Basel,

Schweiz

3Pathologie, Universitätsspital Basel , Basel, Schweiz

Purpose: Manipulation of the immune system by tumors leads to com-

promised antigen recognition and an immunosuppressive microenviron-

ment. One immunomodulatory strategy employed by malignant tumors

is expression of the programmed cell death receptor 1 ligand (PD-L1), the

receptor for which is expressed on activated T cells (PD-1). Expression of

PD1 and PD-L1 in the tumor has prognostic importance in a variety of

malignancies and can predict response to so-called immune checkpoint

inhibitors directed against PD-1 or PD-L1.

Hepatocellular carcinoma (HCC) is the most common primary liver

malignancy, and targeted therapies against this tumor are rare.

e aim of our study was to investigate the impact of PD-1 and PD-L1

expression on HCC recurrence.

Methods: Immunohistochemical staining against PD-1 (NAT105) and

PD-L1 (Ventana SP263) was performed on tissue from 91 postopera-

tive HCC patients. Tumors were classied as immunologically active,

excluded or deserted. PD-1 and PD-L1 immunoreactivity was evaluated

as the proportion of positive staining of the total number of immune cells

(0%, <1% and >1%).

Results: HCC recurrence was signicantly associated with the

immune-excluded subclass. e majority of non-recurrent HCC showed

PD-1 expression >1% (80%; 37/46). Conversely, recurrent HCC showed

PD-1 expression 0% or <1% in 45% (20/45) of the cases. Of note, HCC

classied as immune active were enriched for PD-1 >1% positive cells

(74%; 46/62). No association was found between PD-L1 expression on

tumor cells and HCC recurrence.

Discussion: In concordance with previous reports we found an asso-

ciation between low frequency of PD-1 expression and increased HCC

recurrence. Our results regarding the lack of impact of PD-L1 expression

on HCC recurrence are in line with previous studies in the literature. In

addition, our results suggest that HCC recurrence may be more frequent

in immune-exclusive tumors.

Conclusions: Our results show a higher rate of recurrence in patients

with fewer PD-1 positive tumor inltrating lymphocytes. e expression

of PD-L1 does not seem to be a prognostic marker in HCC.

Disclosure Statement: e authors declare no conict of interest.

296

Clinical scale production of BCMA CAR T cells comprising a

dened early memory phenotype

Jara J. Joedicke1; Ulrich Großkinsky1; Uta E. Höpken2; Armin Rehm1

1Max-Delbrück-Center for Molecular Medicine, Department of Translational

Tumorimmunology, Berlin, Deutschland

2Max-Delbrück-Center for Molecular Medicine, Department of

Microenvironmental Regulation in Autoimmunity and Cancer, Berlin,

Deutschland

Background: Clinical studies on CAR T cells targeting B cell neoplasm

have shown remarkable success rates. However, frequent relapses and

primary refractoriness remain challenging. Dening CAR T cell starting

populations, can prevent production failure, yield a more homogenous

CAR T cell product, and thereby prevent early remission aer CAR T cell

therapy.

Methods: To produce early memory BCMA CAR T cells we combined the

fully-closed bioreactor system CliniMACS Prodigy with an S2 cell sorter.

Apheresis material was introduced into the Prodigy, depleted of RBCs and

MACS puried for CD4+/CD8+ cells. e cells were retrieved from the

system, antibody-stained for CD62L/CD95 and FACS sorted for double

positive cells under aseptic conditions. e puried early memory T cells

were reapplied to the Prodigy system. Subsequently, T cells were activated,

γ-retrovirally transduced with a BCMA-CAR encoding SIN vector and

expanded in a memory enhancing cytokine milieu.

Result: Sorting and subsequent culture in IL7/IL15 containing medium

resulted in an increased early memory phenotype in both CD4+ and CD8+

CAR T cells, when compared to bulk runs. Despite lower starting cell

numbers of highly enriched early memory T cells, the process resulted in

clinically relevant CAR T cell yields with maintained eector functions.

Discussion: With our newly established protocol, combining the Prodigy

with an aseptic sorting step, we showed the successful production of func-

tional BCMA CAR T cells with an early memory phenotype from a lim-

ited number of starting T cells.

Conclusion: We developed an economic and safe production protocol for

dened CAR T cell populations at a clinical scale.

Disclosure Statement: e authors declare no conict of interest.

307

Extracorporal photopheresis for immune-related adverse

events after checkpoint inhibitor treatment – a multicenter

survey

Petya Apostolova1; Jan-Malte Placke2; Susanne Unger3; Sophie Giesler1;

James Hutchinson4; Sebastian Haferkamp5; Theresa Lowinus1;

Justus Duyster1; Carolin Funke-Lorenz2; David Rafei-Shamsabadi6;

Frank Meiss6; Burkhard Becher3; Robert Zeiser1

1Medical Center, Albert-Ludwigs University, Freiburg, Germany, Department of

Medicine I, Faculty of Medicine, Freiburg, Deutschland

2University of Essen, Department of Dermatology, Essen, Deutschland

3Institute of Experimental Immunology, University of Zurich, Zürich, Schweiz

4University Hospital Regensburg, Regensburg, Department of Surgery,

Regensburg, Deutschland

5University Hospital Regensburg, Regensburg, Department of Dermatology,

Regensburg, Deutschland

6Medical Center – University of Freiburg, Department of Dermatology, Freiburg,

Deutschland

Treatment with immune checkpoint inhibitors (ICI) has improved the

long-term prognosis of many patients with metastatic tumors. However,

immune-related adverse events (irAE) occur in up to 50% of all ICI-

treated individuals. Treatment of irAE consists of glucocorticosteroids,

other immunosuppressive agents and interruption of ICI-based immu-

notherapy. ese approaches are based on clinical experience rather than

on prospective phase-III trial data. 20-50% of the irAE patients do not

achieve a complete remission upon glucocorticosteroid therapy, or expe-

rience irAE relapse when immunosuppressive medication is tapered. We

have previously described the successful treatment of checkpoint inhibi-

tor-induced colitis with extracorporeal photopheresis (ECP) (Apostolova

NEJM 2020). Here, we present a retrospective survey on the use of ECP

for the treatment of irAE. Seven patients were treated at three dierent

cancer centers between April 2018 and August 2021, for ICI-related colitis

(7/7 patients, 100%) and arthralgia (1/7 patients, 14.3%). e underly-

ing malignancies included melanoma (6/7 patients, 85.7%) and renal cell

cancer (1/7 patients, 14.3%). e median duration of ECP treatment was

22 weeks, and the median number of ECP-procedures was 16. Complete

resolution of irAEs occurred in six of seven patients (85.7%) and one

patient was stabilised following ECP. e median time to response was 14

days. ree patients discontinued immunosuppression completely while

on ECP, whereas immunosuppressive therapy was reduced by 43% - 88%

in the other four patients. No serious adverse events were associated with

ECP. Tumor progression occurred in one patient, the other six patients

had an ongoing tumor control (CR n=3; PR n=2, SD n=1) during ECP

treatment.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts52

Our results indicate that ECP for irAE is safe and has clinical activity in

a real-world setting. Deep proling of immune cell population pheno-

type and metabolism is planned in order to decipher how ECP controls

immune pathology leading to the clinical resolution of irAE.

Disclosure Statement: e authors declare the following:

R.Z.: Honorar für Vorträge von Novartis, Incyte und MNK

329

Anti-EMMPRIN antibody h161-pAb disrupts

epithelial-mesenchymal transition in breast and oral

cancercells: a targeted approach to inhibit metastasis

Phillipp Brockmeyer1; Felix Oyelami2,3; Elina Simanovich2;

HenningSchliephake1; Michal A. Rahat2,3

1Department of Oral and Maxillofacial Surgery, University Medical Center

Göttingen, Göttingen, Deutschland

2The Immunotherapy Laboratory, Carmel Medical Center, Haifa, Israel

3The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Background: Metastasis is the main reason for cancer-related deaths.

Epithelial-mesenchymal transition (EMT) enhances tumor cell motility

and invasiveness which is critical for metastasis. Tumor associated mac-

rophages (TAMs) secret EMT inducing cytokines. Molecules mediating

TAM-tumor cell interactions and promoting EMT are not well known.

Transmembranal protein EMMPRIN has been implicated in EMT and

could be a target for an antimetastatic therapy approach.

Methods: Human monocytic cell line U937 was co-cultured with human

breast carcinoma cells (MCF7 or MDA-MB-231) or oral carcinoma cells

(SCC40 and PCI-13), with or without the addition of the newly developed

anti-EMMPRIN antibody h161-pAb. EMMPRIN expression and secre-

tion (IF, WB, ELISA), E-cadherin and vimentin expression (WB, IF), and

cell migration and proliferation (scratch assay, CCK-8) were monitored.

Result: Co-culturing reduced E-cadherin expression in the epithelial-like

MCF7 and SCC40 cells and enhanced their migration relative to the sin-

gle cultures. In contrast, mesenchymal-like cells (MDA-MB-231 or PCI-

13) did not change vimentin expression or their migration. Secretion of

EMT inducers (primarily TGFβ, also TNFα, IGF-1 and EGF, the latter

only in breast cells) was enhanced in all co-cultures. Although EMMPRIN

expression and secretion were unchanged, its activities, including prolifer-

ation and induction of VEGF and MMP-9 secretion, were increased in all

co-cultures, whereas migration was increased only in the epithelial cells.

When h161-pAb was added to the co-cultures, proliferation, migration,

the levels of EMT-inducers and the secretion of VEGF and MMP-9 were

reduced, and vimentin expression was decreased in the mesenchymal-like

cells.

Discussion: Monocytes and EMMPRIN might be important during

metastasis. EMT properties partially overlap with EMMPRIN activity.

H161-pAb reduced the mesenchymal properties of the tumor cellss.

Conclusion: Blocking EMMPRIN activity with h161-pAb may be useful

to decrease metastasis.

Disclosure Statement: e authors declare no conict of interest.

560

Ecacy and Safety of Idecabtagene vicleucel (ide-cel, bb2121)

in Elderly Patients (Pts) with Relapsed and Refractory Multiple

Myeloma (RRMM): KarMMa Subgroup Analysis

Hermann Einsele1; Jesús Berdeja2; Noopur Raje3; David Siegel4; Yi Lin5;

Larry Anderson; Jr6; Paula Rodriguez-Otero7; Salomon Manier8;

Michele Cavo9; Anna Truppel-Hartmann10; Everton Rowe11; Jill Sanford11;

Julie Wang11; Timothy Campbell11; Sundar Jagannath12

1University Hospital of Würzburg, Würzburg, Deutschland

2Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA

3Massachusetts General Hospital, Boston, USA

4Hackensack University Medical Center, Hackensack, USA

5Mayo Clinic, Rochester, USA

6UT Southwestern Medical Center, Simmons Comprehensive Cancer Center,

Dallas, USA

7Clínical Universidad de Navarra, Pamplona, Spanien

8Service des Maladies du Sang, CHU Lille, Lille, Frankreich

9Seràgnoli Institute of Hematology, Bologna University School of Medicine,

Bologna, Italien

10bluebird bio, Cambridge, USA

11Bristol Myers Squibb, Princeton, USA

12Mount Sinai Medical Center, New York, USA

Background: Advanced age negatively aects prognosis and limits treat-

ment options in pts with multiple myeloma. Idecabtagene vicleucel (ide-

cel, bb2121), a BCMA-directed CAR T cell therapy, showed frequent,

deep and durable responses in the pivotal phase 2 KarMMa study of pts

with triple-class exposed RRMM.1 Here we report updated ecacy and

safety data for ide-cel in elderly pts enrolled in the KarMMa study.

Methods:Pts in the KarMMa trial (NCT03361748) had ≥3 prior lines of

therapy, including an immunomodulatory agent, a proteasome inhibi-

tor, and an anti-CD38 monoclonal antibody, and were refractory to their

last regimen per International Myeloma Working Group (IMWG) crite-

ria. Pts received ide-cel at 150–450 × 106CAR+ T cells aer 3 d of lym-

phodepletion followed by 2 d of rest. e primary endpoint was overall

response rate (ORR). Pts were classied into ≥65 y and ≥70 y subgroups

for analysis. Responses were assessed using IMWG guidelines; duration of

response (DOR) and progression-free survival (PFS) were analyzed with

Kaplan-Meier methods.

Results:Of 128 ide-cel–treated pts, 45 (35%) were ≥65 y and 20 (16%)

were ≥70 y of age. Median age in these age groups was 69 y (range, 65–78)

and 73 y (range, 70–78), and median number of prior antimyeloma reg-

imens was 6 and 5, respectively. At data cuto (21 Dec 2020), response

rates and DOR for both age groups were similar to the overall ide-cel–

treated population; ORR was 84% and 90%, complete response rate was

31% and 35%, and median DOR among responders was 10.9 mo and 11.0

mo in pts aged ≥65 y and ≥70 y, respectively. Median PFS was 8.6 mo (95%

CI, 4.9–12.3) in pts aged ≥65 y and 10.2 mo (95% CI, 3.1–12.4) in pts aged

≥70 y. No new safety signals were identied.

Discussion: ese data suggest that older age (≥70 y) does not signi-

cantly impact PFS following ide-cel treatment.

Conclusions:Ide-cel continues to demonstrate benet with a manageable

safety prole in triple-class exposed pts with RRMM aged ≥65 y and ≥70y.

Outcomes were comparable with the overall ide-cel–treated population.

Reference:

1. Munshi NC, et al.N Engl J Med 2021;384:705–716.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 53

613

The role of TSPO in T cell immune control of glioblastoma

Ayse N. Menevse1; Laura-Marie Ammer2; Arabel Vollmann-Zwerenz2;

Celine Rohrmus2; Marcell Kupczyk1; Markus J. Riemenschneider3;

Nathalie L. Albert4; Peter Bartenstein4; Jörg-Christian Tonn5;

Philipp Beckhove1; Peter Hau2

1RCI Regensburger Centrum für Interventionelle Immunologie, Regensburg,

Deutschland

2Wilhelm Sander NeuroOnkologie , Neurologie, Universitätsklinikum

Regensburg, Regensburg, Deutschland

3Neuropathologie , Universitätsklinikum Regensburg, Regensburg, Deutschland

4Klinik und Poliklinik für Nuklearmedizin , Ludwig-Maximilians-Universität

München, München, Deutschland

5Klinik und Poliklinik für Neurochirugie , Ludwig-Maximilians-Universität

München, München, Deutschland

Background: Glioblastoma (GB) is the most fatal primary brain cancer

in adults. Its malignancy is greatly enhanced by resistance to common

anti-cancer treatments including immunotherapy. Translocator protein

(TSPO) is overexpressed in GB and has been implicated with a functional

role on GB hallmark features including resistance to apoptosis and evad-

ing recognition by the immune system. However, the exact role of TSPO

in GB is unknown. We hypothesize that TSPO contributes to the resis-

tance of GB tumor cells against T cell-mediated killing.

Methods: We established co-cultures of primary brain tumor initiating

cells (BTICs) and allogeneic or autologous T cells. We generated stable

TSPO-knockdown BTICs and measured cytotoxicity and active caspase

3/7 in these co-cultures. In parallel, TSPO-decient BTICs were treated

with apoptosis-inducing cytokines and the eect on the apoptotic cascade

and TSPO expression was evaluated. In addition, we performed RNA

sequencing of TSPO decient versus control BTICs.

Result: TSPO expression was upregulated in BTICs upon contact with T

cells. TNFα and IFNγ were identied as key activators of TSPO expres-

sion. Knockdown of TSPO in BTICs resulted in improved T cell-medi-

ated killing in autologous and allogeneic co-culture settings. BTICs were

resistant to apoptosis inducers TNFα and FasL, whereas TRAIL eectively

activated the apoptotic cascade. More importantly, we showed that down-

regulation of TSPO in BTICs further sensitized cells to TRAIL-induced

apoptosis by activating both intrinsic and extrinsic apoptosis pathways.

Our transcriptome analysis on TSPO decient BTICs revealed downregu-

lated genes that were associated with apoptosis-resistance.

Discussion: Upregulation of TSPO by T cell-derived cytokines might

inuence the therapeutic eect of GB immunotherapy.

Conclusion: Our data provide rst evidence that TSPO is upregulated

upon contact with tumor-reactive T cells. ereby, TSPO may act as resis-

tance mechanism against T cell-mediated apoptosis in GB.

Disclosure Statement: e authors declare no conict of interest.

649

Endogenous T-cell responses to tumor associated antigens are

frequent in esophago-gastric adenocarcinoma and antigen

specic T cells can be expanded using CD40-activated B cells

Martin Thelen1; María García-Márquez1; Jonas Lehmann1;

Diandra Keller1; Ella Preugszat1; Christiane Bruns2; Alexander Quaas3;

Michael von Bergwelt-Baildon4,5,6; Hans Schlößer1,2

1Center for Molecular Medicine Cologne, University of Cologne, Faculty

of Medicine and University Hospital Cologne, Cologne, Germany, Köln,

Deutschland

2Klinik für Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie,

University of Cologne, Faculty of Medicine and University Hospital Cologne,

Cologne, Germany, Klön, Deutschland

3Institute of Pathology, University of Cologne, Faculty of Medicine and University

Hospital Cologne, Cologne, Germany, Köln, Deutschland

4Medizinische Klinik und Poliklinik 3, Ludwig Maximilian Universität München,

München, Deutschland

5Gene Center Munich, Ludwig Maximilians University, Munich, Germany

6German Cancer Consortium (DKTK), Heidelberg, Deutschland

Background: Tumor-associated antigens (TAAs) are major targets of

immunotherapy. erapeutic targeting of TAAs is scalable as they are

shared between patients. Modern cellular therapies, especially those using

combined targeting of multiple antigens have renewed the interest in

TAAs. Our study elucidates the role of TAAs in esophago-gastric adeno-

carcinoma (EGA).

Material and Methods: Nanostring was used to assess expression of 26

TAAs and 25 genes associated with antigen-presentation in tumor sam-

ples and matched normal tissue of 41 treatment-naive EGA patients.

Peptide pools from the 10 most important TAAs were selected and co-cul-

tured with peripheral blood mononuclear cells (PBMCs, n=21) to deter-

mine cellular anti-tumor immune responses in IFN-γ/IL-2 FluoroSpot

assays. e Immune Score was determined using digital image analyses of

immunohistochemical tumor stains (CD3, CD8). Finally, TAA-specic T

cells were expanded using CD40 activated B cells and used to demonstrate

specic killing of tumor cells in-vitro.

Results: CEP55 and MAGEA3/6 showed the highest expression, whereas

expression of NY-ESO-1 was low. 68.3% (28/41) of tumors expressed ≥

5/10 analyzed TAAs simultaneously. Samples with high immune scores

expressed more TAAs and showed higher expression of genes related to

antigen-presentation. TAA-specic immune responses against at least one

TAA were detectable in 75.0% of patients. 6/20 patients showed cellular

responses against ≥5 TAAs simultaneously. We demonstrate feasibility of

TAA-specic T-cell expansion using CD40 activated B cells as a strategy to

induce or enhance TAA-specic immune responses with cytotoxic activ-

ity in EGA. Importantly, endogenous TAA-specic T cell responses were

related to absent expression of the respective TAA in 88.2% of patients.

Conclusion: TAAs are important targets for immuotherapy and immune

monitoring of EGA. Personalized immunotherapeutic strategies target-

ing EGA-specic combinations of TAAs appear highly promising in this

challenging disease. However, additional targeting of immune escape may

be needed.

Disclosure Statement: e authors declare the following:

Advisory Board for BMS; Funding for Research by Astra Zeneca.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts54

681

TCR gene therapy of CD22-positive B cell malignancies

Simone Rhein1; Neşe Çakmak-Görür2; Corinna Grunert2; Elisa Kieback3;

Matthias Leisegang2; Sebastian Ochsenreither2; Antje Siegert4;

Bernadette Brzezicha4; Gerald Willimsky2,5; Ulrich Keller1,2,5;

Thomas Blankenstein1,2; Antonio Pezzutto2; Antonia Busse2

1Max Delbrück Center for Molecular Medicine in Helmholtz Association, Berlin,

Deutschland

2Charité-Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt-Universität zu Berlin, Berlin, Deutschland

3T-knife GmbH, Berlin, Deutschland

4EPO Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin,

Deutschland

5German Cancer Consortium (DKTK), Heidelberg, Germany, Partner Site Berlin,

Berlin, Deutschland

Background: CD22 is a suitable alternative to CD19- and CD20-directed

therapies, as these oen lead to downregulation or loss of antigen. CD22-

targeted chimeric antigen receptor (CAR) T cells induce remission in B

cell acute lymphoblastic leukemia (B-ALL), but its ecacy is oen ham-

pered by downmodulation of surface CD22. Since intracellular CD22

expression is maintained in these cases, malignant cells might still be targ-

etable by a CD22-directed T cell receptor (TCR) cell therapy.

Methods: We used a humanized mouse model that is transgenic for the

human TCR α and β gene loci and the human HLA-A*02:01 to generate

TCR specic for a CD22 epitope. Aer molecular cloning of TCRs, TCR-

transduced T cells were tested for ecacy and specicity in vitro and were

tested in a xenogra mouse model.

Result: Lymphoblastoid cell lines (LCLs) expressing high amounts of sur-

face CD22 are equally recognized by CD22 TCR and CAR, while cells

expressing intracellular CD22 are only recognized by CD22 TCR T cells.

Patient and PDX tumor cells were eciently recognized by the CD22 TCR

T cells. e safety analysis of the lead TCR did not reveal any o-target

eects or alloreactivity: a panel of HLA-A2-negative LCLs and around

100 self-peptides eluted from the human peptidome were not recognized

by CD22 TCR T cells. Using Alanine scan the peptide binding motif was

determined, but no other homologous epitopes could be found in the

human proteome. In a xenogra mouse model with Nalm6 cells there was

a slight ecacy advantage of CD22 TCR over CD22 CAR observed.

Discussion: To further prove the advantage of CD22 TCR over CD22

CAR T cells more primary patient samples have to be tested, preferably

from relapsed patients aer a CD19-CAR T cell therapy or aer treatment

with the CD22-targeting agent inotuzumab ozagamicin.

Conclusion: We have demonstrated the ecacy and safety of our lead

CD22 TCR candidate. As this TCR therapy might have the potential to

eectively treat patients relapsed aer CAR T cell therapy, we pursue the

pre-clinical development.

Disclosure Statement: e author Simone Rhein declares the previous

employment by T-Knife GmbH and is currently employed by Epo GmbH.

e project is funded by a cooperation project between MDC and T-knife GmbH.

All other authors declare no conict of interest.

700

ZENYTH-ESO: Master protocol to assess the safety

and recommended phase II dose of next generation

NY-ESO-1-specic TCR T-cells in HLA-A*02 patients with

synovial sarcoma, myxoid/round cell liposarcoma and non-

small cell lung cancer [Substudy 1 (GSK3901961)

and Substudy 2 (GSK3845097)]

Roland Ullrich1; Martin Wermke2; Jerey Yachnin3; Stephan Mielke4;

Reema Patel5; Melinda L Yushak6; Adam J. Schoenfeld7; Jayesh Desai8;

Mehmet Altan9; Sandra P. D’angelo7; Jonathan Noujaim10; John B.A.G.

Haanen11; Benjamin Powers12; Thomas Faitg13; Wenlei Liu13; Nitin Patel13;

Dejka M. Araujo9

1University Clinic Cologne, Köln, Deutschland

2Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Deutschland

3Karolinska Institutet, Solna, Schweden

4Karolinska University Hospital and Institutet, Stockholm, Schweden

5Markey Cancer Center, Lexington, USA

6Emory Winship Cancer Institute, Atlanta, USA

7Memorial Sloan Kettering Cancer Center, New York, USA

8Peter MacCallum Cancer Centre, Melbourne, Australien

9MD Anderson Cancer Center, Texas, USA

10Institut D’Hématologie-Oncologie, Hôpital Maisonneuve-Rosemont, Montreal,

Kanada

11Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, Niederlande

12University of Kansas Medical Center, Division of Hematology/Oncology,

Department of Internal Medicine, Kansas City, USA

13GlaxoSmithKline, London, Vereinigtes Königreich

Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an

autologous T-cell therapy expressing an anity-enhanced T-cell recep-

tor (TCR) to improve recognition of cancer cells expressing NY-ESO-1

and/or LAGE-1a. GSK3901961 and GSK3845097 are next generation

NY-ESO-1 TCR T-cell therapies. GSK3901961 co-expresses the α-chain

of the CD8 co-receptor to improve T-cell persistence and helper func-

tions. GSK3845097 reduces TGF-β pathway activation and maintains

Tcell proliferation, cytokine production, and cytotoxicity in the tumor

microenvironment.

A rst-time-in-human master protocol (NCT04526509) will evaluate

the safety, tolerability, and recommended Phase 2 dose (RP2D) of NY-ESO-

1-specic TCR T-cell therapies. Substudy 1 will assess GSK3901961 in

advanced non-small cell lung cancer (NSCLC), or advanced synovial sar-

coma (SS) or myxoid/round cell liposarcoma (MRCLS). Substudy 2 will

assess GSK3845097 in advanced SS or MRCLS.

Methods: Each substudy includes a dose conrmation stage to assess RP2D

and a dose expansion stage, aiming to dose 10 participants at the RP2D.

Key inclusion criteria: age ≥18 years; measurable disease per RECIST

v1.1; HLA-A*02:01, A*02:05, or A*02:06 positivity; NY-ESO-1/LAGE-1a

tumor expression; Substudy 1: Stage IV NSCLC, receipt of ≥1 prior line(s)

of standard of care therapy; Substudy 1, and Substudy 2: advanced (met-

astatic/unresectable) SS or MRCLS; and prior anthracycline-based ther-

apy. Key exclusion criteria: prior malignancy not in complete remission or

clinically signicant systemic illness; and central nervous system metas-

tases (SS and MRCLS only). Primary endpoints: safety (adverse events)

and tolerability (dose-limiting toxicities). Secondary endpoints: investiga-

tor-assessed overall response rate, duration of response, and cell kinetics.

Results: e substudies are enrolling.

Discussion: Presented at AACR ’21 and ASCO ‘21. Funding: GSK

(209012; NCT04526509).

Conclusion: is master protocol will evaluate the safety and ecacy of

next generation NY-ESO-1 specic TCR-T cells in SS/MRCLS or NSCLC.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 55

730

Antitumor activity of dostarlimab in patients with advanced

or recurrent mismatch repair–decient or –procient cancer

by prior therapy: Results from the GARNET study

Lars Hanker1; Ana Oaknin2; Lucy Gilbert3; Anna Tinker4; Jubilee Brown5;

Cara Matthews6; Joshua Press7; Renaud Sabatier8; David O’malley9;

Vanessa Samouelian10; Valentina Boni11; Linda Duska12;

Sharad Ghamande13; Prafull Ghatage14; Rebecca Kristeleit15;

Charles Leath III16; Jennifer Veneris17; Tao Duan17; Ellie Im18;

Bhavana Pothuri19

1Universitatsklinikum Schleswig-Holsetin, Lübeck, Deutschland

2Vall d’Hebron University Hospital, Barcelona, Spanien

3McGill University Health Centre Research Institute, Montreal, Kanada

4BC Cancer, Vancouver, Kanada

5Levine Cancer Institute, Atrium Health, Charlotte, USA

6Women and Infants Hospital of Rhode Island, Providence, USA

7Swedish Cancer Institute, Gynecologic Oncology and Pelvic Surgery,

Seattle,USA

8Institut Paoli Calmettes, Marseille, Frankreich

9The Ohio State University James CCC, Columbus, USA

10Université de Montréal, Montreal, Kanada

11Hospital Universitario HM Sanchinarro, Madrid, Spanien

12Emily Couric Clinical Cancer Center, Charlottesville, USA

13Augusta University, Augusta, USA

14University of Calgary, Calgary, Kanada

15University College London, London, Vereinigtes Königreich

16University of Alabama at Birmingham, Birmingham, USA

17GlaxoSmithKline, Waltham, USA

18GlaxoSmithKline (when study was conducted), Waltham, USA

19New York University, New York, USA

Background: Dostarlimab is a humanized programmed death 1 (PD-1)

receptor monoclonal antibody that blocks interactions with PD-1 ligands.

GARNET (NCT02715284) is a phase 1 study assessing antitumor activity

and safety of dostarlimab monotherapy in patients with advanced solid

tumors.

Methods: is multicenter, open-label, single-arm study is conducted in

2 parts: dose escalation and expansion. Patients with advanced or recur-

rent mismatch repair–decient (dMMR) or microsatellite instability–

high (MSI-H) endometrial cancer (EC) or mismatch repair–procient

(MMRp) EC that progressed on or aer a platinum regimen received

dostarlimab 500 mg intravenously Q3W for 4 cycles, then 1000 mg Q6W

until disease progression or discontinuation. Primary endpoints were

objective response rate (ORR) and duration of response by BICR using

RECIST v1.1. Here we report ORR in dMMR/MSI-H and MMRp EC by

prior lines of therapy (LOTs).

Result: Ecacy analyses included 108 dMMR/MSI-H and 142 MMRp

patients. ORR (95% condence interval [CI]) was 43.5% (34.0–53.4) in

dMMR/MSI-H and 13.4% (8.3–20.1) in MMRp. ORR was slightly higher

(47.8%; 95% CI: 35.6–60.2) in patients with dMMR/MSI-H with 1 prior

LOT (n=69) but lower (35.9%; 95% CI: 21.2–52.8) in those who received

≥2 prior LOTs (n=39). In the MMRp population, ORR was 13.8% (6.5–

24.7) in patients with 1 prior LOT (n=65) and 13.0% (6.4–22.6) in patients

with ≥2 prior LOTs (n=77).

Safety has been previously reported.1

Discussion:

Conclusion: Dostarlimab demonstrated antitumor activity in recurrent

or advanced dMMR/MSI-H and MMRp EC regardless of number of prior

LOTs. Patients with dMMR/MSI-H EC who received 1 prior LOT had

slightly higher ORR than those who received ≥2 prior LOTs.

Reference:

1. Oaknin A, et al. Ann Oncol 2020;31(suppl 4):S1142–S1215

is abstract was previously presented at the International Gynecologic Cancer

Society 2021 Annual Meeting and is submitted on behalf of the original authors

with their permission.

Funding: GSK 213346; editorial support from Fishawack Indicia Ltd., UK, part of

Fishawack Health and funded by GSK.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Endocrine Tumors (e. g. thyroid cancer, adrenal tumor, neuroendocrine tumor)

Poster

277

Selpercatinib ecacy and safety in patients with RET-altered

thyroid cancer: a clinical trial update

Eric Sherman1; Lori Wirth2; Manisha Shah3; Maria Cabanillas4; Bruce

Robinson5; Antoine Italiano6; Janessa Laskin7; Vivek Subbiah4; Alexander

Drilon8; Jennifer Wright9; Pearl French9; Victoria Soldatenkova9;

MatthiasKroiss10; Daniela Weiler11

1Memorial Sloan Kettering Cancer Center

2Massachusetts General Hospital, Boston, USA

3Ohio State University Comprehensive Cancer Center, Columbus, USA

4University of Texas M.D. Anderson Cancer Center, Houston, USA

5Royal North Shore Hospital, St. Leonards, Australien

6University of Bordeaux, Bordeaux, Frankreich

7British Columbia Cancer Agency, Vancouver, Kanada

8Memorial Sloan Kettering Cancer Center, New York, USA

9Eli Lilly and Company, Indianapolis, USA

10Universitätsklinikum Würzburg, Würzburg, Deutschland

11Cantonal Hospital, Luzern, Schweiz

Background: We report an update of selpercatinib’s (a highly selective and

potent RET kinase inibitor) ecacy and safety results in RET-altered thy-

roid cancer, with a longer follow-up (30-Mar-2020 data cuto vs 16-Dec-

2019) and additional enrolment.

Methods: Patients (pts) with RET-mutant medullary thyroid cancer

(MTC) and RET-fusion positive thyroid cancer (TC) were enrolled in

global (16 countries, 89 sites) Phase 1/2 LIBRETTO-001 trial. Primary

endpoint: objective response rate (ORR). Secondary endpoints included

duration of response (DoR), progression-free survival (PFS), clinical ben-

et rate (CBR; CR+PR+SD ≥16 weeks) and safety. e integrated analysis

set (IAS, n=143) includes ecacy evaluable MTC pts previously treated

with cabozantinib and/or vandetanib (cabo/vande). e primary analysis

set (PAS), a subset of IAS, is the rst 55 enrolled pts. Cabo/vande naïve

MTC pts (N=112) and TC pts with prior systemic treatment (N=22) were

also analyzed. Safety population includes all pts who received ≥1 dose

(MTC N=315; TC N=42) by data cuto.

Result: For MTC patients, ORR% (95%CI) was 69.2 (61.0, 76.7) for IAS

(n=143), 69.1 (55.2, 80.9) for PAS (n=55) and 71.4 (62.1, 79.6) for cabo/

vande-naïve MTC pts (n=112). ORR% (95%CI) for TC pts (n=22) was

77.3 (54.6, 92.2). Most treatment-emergent adverse events (TEAEs) were

low grade; most common (≥25% MTC and/or TC pts treated with selp-

ercatinib) were dry mouth, diarrhea, hypertension, fatigue and constipa-

tion for both MTC and TC pts, increased ALT/AST, peripheral edema

and headache in MTC pts and nausea in TC pts. 4.8% MTC and TC pts

discontinued selpercatinib due to TEAEs; only 1.9% with MTC and none

with TC discontinued due to treatment-related adverse events.

Discussion: Selpercatinib continues to show marked and durable antitu-

mor activity in pts with RET-altered thyroid cancers. It is well tolerated

and no new safety concerns are identied.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts56

Conclusion: A global, randomized, phase 3 trial (LIBRETTO-531) eval-

uating selpercatinib vs cabo/vande in kinase inhibitor-naïve MTC pts is

ongoing.

Disclosure Statement: e authors declare the following: Vortragshonorar Lilly

Deutschland GmbH (persönlich bzw. Institution) Beraterhonorare Lilly Deutsch-

land GmbH Prüfer in klinischen Studien zu Selpercatinib LOXO Oncology

(Libretto-001-Studie) LOXO at Lilly (Libretto-201-Programm) Lilly (Libret-

to-531-Studie)

403

Mechanisms of CUX1-induced Tumor Progression in

Neuroendocrine Tumors of the Pancreas

Maryam Khosravian1; Stefanie Göllner1; Julia Weißbach1; Danny Misiak2;

Helmut Laumen1; Patrick Michl1; Sebastian Krug1

1University Hospital Halle (Saale), Department of Internal Medicine I, Martin

Luther University Halle-Wittenberg, Halle (Saale), Deutschland

2Department for Molecular Cell Biology, Institute for Molecular Medicine, Martin

Luther University Halle-Wittenberg, Charles-Tanford-Proteinzentrum, Halle

(Saale), Deutschland

Background: Pancreatic neuroendocrine tumors (PanNET) are a group

of heterogeneous malignancies. We previously identied the transcrip-

tion factor Cut homebox 1 (CUX1) as an important mediator of tumor

progression and therapy resistance in PanNET. Based on our preliminary

data, the aim of this work is to characterize the underlying molecular

mechanisms of CUX1-induced tumor progression to identify potential

targets for therapeutic intervention.

Method: In the two PanNET cell lines BON-1 and QGP1 transient CUX1

knockdown was performed by transfecting cells with siRNAs. For stable

knockdown, CUX1 oligonucleotides corresponding to gene specic small

hairpin RNA sequences were cloned into the pGreenPuro lentivector.

e CUX1-p200 gene was cloned into the pCDH overexpression vector.

Western blotting assay was used to investigate CUX1 expression levels. To

assess eect on apoptosis, TUNEL assay was used. RNA sequencing was

performed to provide insight into the transcriptome of PanNETs. To fur-

ther characterize the impact of CUX1 KD, gene set enrichment analysis

(GSEA) based on sequencing data was accomplished.

Result: Transiently CUX1 KD in PanNET cells showed an upregulation

of apoptosis. e RNA sequencing data displayed numbers of mRNAs,

lncRNAs and miRNAs, which are dierentially expressed (FDR < 0.05)

upon CUX1 KD. STC1, LINC02404 and hsa-miR-1197 are interesting

candidates that are upregulated with CUX1 KD. GSEA identied E2F tar-

gets, G2M checkpoint as well as MYC targets as top depleted and hypoxia,

oxidative phosphorylation and TNFA signaling as top-enriched pathways

in CUX1 KD cells.

Discussion and conclusion: Our results suggest that CUX1 could behave

as an oncogenic factor in PanNET via modulating a complex network of

protein-coding and non-coding RNAs. Further experiments such as mass

spectrometry, lncRNA pull down and miRNA knockdown are needed to

elucidate the mechanisms in detail and to propose targets for therapeutic

intervention in CUX-1 overexpressing PanNET.

Disclosure Statement: e authors declare no conict of interest.

579

Papillary thyroid cancer and its neoplastic variants –

connection with the genomic prole, cyto/hystopathological

ndings and clinical presentation

Darko Katalinic1; Ivan Aleric1; Aleksandar Vcev1; Ante Škaro2;

Irena Ranogajec3

1Faculty of Dental Medicine and Health and Faculty of Medicine, J.J. Strossmayer

University, Osijek, Kroatien

2Leptir Clinic, Zagreb, Kroatien

3Sveti Duh Clinical Hospital, Zagreb, Kroatien

Background: Papillary thyroid cancer (PTC) accounts for approximately

80% of all thyroid cancers and is dened by its unique cytologic and his-

tologic features. Mutations of the RET and BRAF/V600 genes are found

in nearly 70% of PTC cases. ey are able to trigger the activation of

mitogen-activated protein kinase pathway and to promote neoplastic cell

proliferation. Genetic events may further lead to numerous dierent cell

variants of PTCwhich may be identied via the dierent cyto/histopatho-

logic features. e most common are the classical (CV), tall cell (TCV)

and follicular variant (FV). e aim of the study was to perform the geno-

myc analysis of the RET and BRAF(V600) mutations as well as to compare

the obtained results with clinical ndings.

Methods: e study included 112 patients, aged 49-74 years. Mutations

of the RET and BRAF(V600) genes were detected using Real-time poly-

merase chain reaction. Diagnosis of the PTC and its variants was con-

rmed with cyto/histopathological examination.

Result: e most important genomic, cyto/histopathological and prog-

nostic elements regarding all three variants of the PTC: CV-PTC (n=78):

RET and BRAF(V600) mutations are common ndings, with BRAF(V600)

conrming a worse prognosis. e 65% of these patients have shown sta-

bile disease course, with25% with metastatic nodes; TCV-PTC (n=8):

Aggressive behavior has been attributed to BRAF(V600) mutation.

FV-PTC (n=26): Absence of BRAF(V600) mutation was the most import-

ant genetic element.

Discussion: PTC has an excellent prognosis, but certain variants express

more aggressive clinical course. CV-PTC: BRAF(V600) mutation was neg-

ative prognostic element. TCV-PTC presents mostly in older patients, has

a greater propensity for locoregional dissemination and has more aggres-

sive course than CV-PTC; e prognosis of FV-PTC has been similar to

that of CV-PTC.

Conclusion: Our study suggests that PTC is etiopathogenically complex

disease and requires further molecular investigations. e patients with

CV-PTC and FV-PTC had fovorable clinical course comparing to those

with TCV-PTC.

Disclosure Statement: e authors declare no conict of interest.

781

Rare coincidental diagnosis of simultaneous isolated

extrapulmonary sarcoidosis and low-grade thyroid carcinoma

Frank Meyer; Roland S. Croner; Manuela Petersen

Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg,

Deutschland

Background: Sarcoidosis is a rare granulomatous multi-locular, systemic

disease of not completely known etiopathogenesis with substantial het-

erogeneity. Typically, it is associated with the lung, but can become man-

ifest in various organs.

Aim: To illustrate the rare constellation of a simultaneous isolated

extrapulmonary sarcoidosis in the thyroid gland & a poorly dierentiated

thyroid carcinoma

Methods: Scientic case report - data was obtained from routine medical

records.

Result: A 30-years old woman presented with progressive swelling at the

right neck & increased serum thyroglobulin (632 ng/mL). Ultrasonically,

an inhomogeneous node (size, 37x30x35 mm) of the right thyroid gland

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 57

with echo-poor parts & peripheral vascularization was seen; scintigra-

phy showed marginally compensated unifocal autonomy of the thyroid

gland. Right hemithyroidectomy conrmed a nodous structure of thyroid

parenchyma w/o suspicious lymph nodes. Histologically, a 33mm follic-

ular, nodular, encapsulated structure of thyroid parenchyma diagnosed

as follicular adenoma was rst described. External pathological review

reclassied this structure as poorly dierentiated carcinoma of the thyroid

gland with angio-inltrating growth & granulomatous inammation of

sarcoidosis type. According to tumor-board recommendation, complet-

ing thyroidectomy was performed with subsequent ablative radioactive

iodine therapy. Final tumor characteristics were pT2 pN0(0/1) V1 L0 G3

R0. 18F-FDG-PET-CT scan & bronchoscopy showed no further manifes-

tation of sarcoidosis.

Discussion: Extrapulmonary manifestations of sarcoidosis can occur

both w/ & w/o pulmonary manifestation. e simultaneous occurrence of

a thyroid carcinoma & an isolated sarcoid of the thyroid has not yet been

described in the literature.

Conclusion: Incidental ndings of extrapulmonary granulomas should

result in further investigation to identify additional manifestations & to

exclude orid infection or other granulomatous processes. erapy is only

indicated in symptomatic organ manifestations.

Disclosure Statement: e authors declare no conict of interest.

Epidemiology

Best-of-Abstract-Vortrag

452

Inuence of the COVID-19 pandemic on the incidence, stages

and treatment of cancer

Elisabeth C. Inwald1; Michael Gerken2,3; Armin Pauer2,3;

Monika Klinkhammer-Schalke2,3; Olaf Ortmann1

1University Medical Center Regensburg, Department of Gynecology and

Obstetrics, Regensburg, Deutschland

2Tumour Center, Institute for Quality Management and Health Services

Research, University of Regensburg, Regensburg, Deutschland

3Bavarian Cancer Registry – Regional Centre Regensburg, Bavarian Health and

Food Safety Authority, Regensburg, Deutschland

Background: e eects of the COVID-19 pandemic on incidence, stage

distribution, primary therapy, and delay in therapy were analyzed for

breast cancer, prostate cancer, colorectal cancer, bronchial cancer, lym-

phoma and leukemia.

Methods: e years 2020 versus 2019 were compared with focus on the

months of the rst wave of pandemics from February to May 2020 analyz-

ing data from the clinical cancer registry Regensburg.

Result: e total numbers of annual new cases were lower in all entities in

2020 vs. 2019. e percentage decrease ranged between -1.9% for breast

cancer and -15.3% for colorectal cancer, with highly signicant dierence

for colorectal cancer (p<0.001). e comparison of the monthly reported

number of cases showed a decrease in all analyzed cancer entities, in

March to May 2020 compared to 2019 with statistical signicance. ere

was no signicantly increased rate of patients with advanced stages III/IV,

larger tumors T3/T4, positive node status or distant metastases in nearly

all entities neither in the annual nor the monthly comparison. Colorectal

cancer was an exception, with signicantly increased rates in March and

April 2020. Apart from bronchial cancer, rates of primary therapy in

stages I-III in 2020 were mostly slight, but not signicantly lower than in

2019. Signicantly lower treatment rates were found for prostate cancer

in March 2020 and for colorectal cancer in November 2020. e mean

interval between diagnosis and start of therapy was the same or slightly

longer in 2020, but not signicant, except for lung cancer, leukemia and

lymphoma.

Discussion: A potential lack in transmitted medical informations, a delay

of documentation and consequently restricted real-time analysis must be

considered when using data from clinical cancer registries.

Conclusion: A decreased incidence especially during the rst wave

could be shown. A shi of stage distribution and treatment delay was not

observed. Follow-up analyses and observation of the subsequent pan-

demic waves are necessary to conrm the current results.

Disclosure Statement: e authors declare no conict of interest.

Poster

531

Eectiveness of Care in Certied Cancer Centers (WiZen) -

Success of Data Linkage between SHI and Clinical Cancer

Registries

Christoph Bobeth1; Kees Kleihues-van Tol2; Martin Rößler1;

Veronika Bierbaum1; Michael Gerken3; Christian Günster4;

Patrik Dröge4; Thomas Ruhnke4; Monika Klinkhammer-Schalke2,3;

Jochen Schmitt1; Olaf Schoer1

1Universitätsklinikum Carl Gustav Carus Dresden, Zentrum für Evidenzbasierte

Gesundheitsversorgung (ZEGV), Dresden, Deutschland

2Arbeitsgemeinschaft Deutscher Tumorzentren e.V., Berlin, Deutschland

3Tumorzentrum Regensburg, Regensburg, Deutschland

4Wissenschaftliche Institut der AOK (WIdO), Berlin, Deutschland

Background: e project “Eectiveness of care in certied cancer cen-

ters” (WiZen), funded by the Innovation Fund, explores certications in

oncology. e project uses nationwide data from SHI and clinical cancer

registries from four states covering the years 2006-2017. To combine the

strengths of both data sources these are linked for eight dierent cancer

entities in accordance with data protection regulations.

Methods: Data linkage was performed using indirect identiers and vali-

dated using the health insurance ID number as a direct identier and gold

standard. is allowed for quantication of the potential and quality of

dierent linkage variants. Sensitivity and specicity as well as matching

accuracy and precision were used as criteria for the evaluation of the link-

age alternatives. e distributions of relevant variables resulting from the

linkage were validated against the original distributions in the individual

datasets.

Result: Depending on the combination of indirect identiers, the range

of linkage matches was 19,854 to 1,860,145. Near-perfect indirect linkage

of the considered data was achieved by combining information on entity,

date of birth, gender, and zip code of the patients. A total of 62,868 one-

to-one linkages were achieved with the above characteristics and a median

hit quality of more than 97% related to the gold standard for the entities.

e age and sex distributions of the various data sources also showed a

high degree of agreement.

Discussion: SHI and cancer registry data can be linked with high inter-

nal and external validity at the level of the individuals. e stable linkage

allows for entirely new analyses due to simultaneous access to variables

from both data sets (“the best of both worlds”): For individual patients,

both information on UICC stage of disease from the registries and comor-

bidities from SHI data are now available.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts58

Conclusion: Due to the use of readily available linkage variables and the

high success of assignment, our linkage has model character for future

linkage methods in health services research.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

612

Secondary immunodeciency diagnosis in patients with

oncological diseases in Germany

Karsten Franke1; Manfred Welslau2; Christoph Hirche3; Stephan Kaiser3;

Christian Schindler4; Dennis Häckl4

1Institut für Klinische Immunologie, Marien Kliniken Siegen, Siegen, Deutschland

2Onkologisches Zentrum Aschaenburg, Klinikum Aschaenburg-Alzenau,

Aschaenburg, Deutschland

3Takeda Pharma Vertrieb GmbH & Co. KG, Berlin, Deutschland

4WIG2 GmbH, Leipzig, Deutschland

Background: Severe or recurring infections are a common complication

in immunocompromised patients. While a primary immunodeciency

(PID) can be the cause, signicantly more patients suer from a second-

ary immunodeciency ((SID) due to certain underlying diseases) and its

treatments. is claims data analysis describes the prevalence of SID in

the German statutory health insurance (SHI) system and investigates SID

in the subset of patients with specic oncological diseases (e.g. multiple

myeloma (MM) or chronic lymphocytic leukemia (CLL)).

Methods: We used German SHI claims data from almost 4 million patients

from 2013 to 2019. To investigate the prevalence of SID, we selected

patients with certain underlying diseases and included those with ICD-

10-GM codes for immunodeciency proposed by [1], following diagno-

sis of the underlying condition. e analyzed subset of cancer patients

included patients diagnosed with ICD-10 C81 – C92. For incidence and

prevalence evaluation coding of immunodeciency aer diagnosis of the

oncological disease was required.

Results: Extrapolated to the German SHI population, 25,686 patients had

SID in 2019, with prevalence slightly increasing over time. Around 41.5%

of SID patients suered from an underlying oncological disease (e.g.

19.2% had CLL, 12.0% had MM).

SID coding was strikingly low: only 4.4% of the selected cancer patients

had an SID diagnosis, while 33.8% had at least one severe or at least three

recurring infections within four consecutive quarters.

Discussion: Severe or frequently recurring infections occur in more than

one third of all cancer patients. However, secondary immunodeciency is

rarely diagnosed and may result in patients not receiving guideline-ade-

quate care.

Conclusion: SID appears to be underdiagnosed in cancer patients, demon-

strating the need for improved diagnostics and therapeutic strategies.

Indication of source:

1. Zi Zentralinstitut für die Kassenärztliche Versorgung in Deutschland (2020).

Zi-Kodier-Manual Infektanfälligkeit und Immundefekt.

Disclosure Statement: e authors declare the following: Wirtschaliche

Verbindungen

618

Gastroenteropancreatic neuroendocrine neoplasms –

site-specic trends in Bavaria, Germany

Nina Grundmann; Amir Hakimhashemi; Sven Voigtländer; MartinMeyer;

Jacqueline Müller-Nordhorn

Bayerisches Krebsregister, Bayerisches Landesamt für Gesundheit und

Lebensmittelsicherheit (LGL), Nürnberg, Deutschland

Background: Neuroendocrine neoplasms (NEN) are rare and heteroge-

neous tumours, occurring throughout the body. Treatment and prognosis

are mainly determined by NEN localization and histology. Forgastroen-

teropancreatic (GEP) NEN, rising incidence rates were reported for the

last decades, with underlying causes remaining largely unexplained.

Methods: Incident cases of GEP NEN diagnosed between 2005 and 2019

were retrieved from the Bavarian Cancer Registry and stratied for neu-

roendocrine tumours (NET) and neuroendocrine carcinoma (NEC). We

calculated age-standardized incidence rates for all GEP NEN localizations

(International Classication of Diseases, Tenth Revision (ICD-10), codes

C15-C25) and used an annual percentage change (APC) approach includ-

ing a joinpoint analysis to investigate site- and sex-specic trends.

Result: Over the study period, we observed a strong increase of inci-

dence rates for GEP NEN until 2012 (APC 2005-2012: 10.0%) followed

by a slight rise aerwards (APC 2012-2019: 1.8%). Age-standardized rates

of GEP NEN rose from 2.2/100,000 in 2005 up to 4.8/100,000 in 2019.

e increase was mainly driven by the rise of NET from 2008 onwards

(APC 2005-2008: -12.9%; APC 2008-2012: 34.3%; APC 2012-2019: 6.8%).

In contrast, NEC incidence rates rose from 2005 to 2010 (APC: 12.1%)

and decreased from 2010 to 2019 (APC: -7.3%). e highest increase

of NEN incidence rates was found for the stomach (APC: 7.6%; from

0.3/100,000 in 2005 to 0.6/100,000 in 2019) and the pancreas (APC: 7.1%;

from 0.4/100,000 to 1.2/100,000, respectively). NEN rates also rose in the

appendix, the rectum and the small intestine. Trends were similar for men

and women.

Discussion: Continuously rising incidence rates of GEP NEN indicate

an increase in the burden of NEN. However, this increase may partially

be attributable to an increased use of advanced imaging techniques and

endoscopic procedures.

Conclusion: Further research including stage-specic analyses is needed

to better understand trends in NEN incidence.

Disclosure Statement: e authors declare no conict of interest.

639

Modeling age-specic incidence of colon cancer via niche

competition

Steen Lange; Richard Mogwitz; Denis Huenniger; Anja Voß-Böhme

Hochschule für Technik und Wirtschaft Dresden (HTW Dresden), Fakultät

Informatik/Mathematik, DataMedAssist, Dresden, Deutschland

Background: Cancer development is a multistep process oen starting

with a single cell turning into a tumor cell due to genetic and epigene-

tic alterations, whose progeny growths via clonal expansion into a mac-

roscopic tumor with billions of cells. While experimental insight exists

on the cellular scale and cancer registries provide statistics on detectable

tumors, the complex dynamics leading from the microscopic cellular scale

to a macroscopic tumor is still not fully resolved. e study ‚Modeling

age-specic incidence of colon cancer via niche competition‘ aims to con-

nect these to two regimes of cancer development.

Methods: We use a cell-based Moran model, which focuses on the com-

petition between wild-type and tumor cells in colonic crypts, to repro-

duce epidemilogical age-specic incidence rates of colon cancer fom the

SEER database. All model parameters are directly set by known physio-

logical parameters and only the eective replacement rate in the crypt is

calibrated.

Result: e model predictions match the epidemilogical rates, even at

ages below 30, where rates are orders of magnitude smaller. e model

predictions are also consistent with the common clinical estimates that

more than 95% of colon adenocarcinomas arise from colonic polyps and

that the fraction of benign tumor is over 99%. Model prediction and epi-

demiological incidence rates agree analogously for rectal cancer.

Discussion: In contrast to previous models, which require four or more t

parameters to reproduce epidemiological incidence rates, our model only

requires a single time scale to be calibrated.

Conclusion: e predictive power of the pretumor progression model

strongly suggests that the fate of tumor development is dominated by

the early phase of tumor development long before a tumor becomes

detectable.

Disclosure Statement: e authors declare no conict of interest. e authors

work at a technical college and the work is co-funded by the EU, the European

Social Fund (ESF) and by tax funds on the basis of the budget passed by the

Saxonstate parliament.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 59

675

Municipal solid waste landll sites and cancer risk in Germany

Isabelle Finke, Stephanie Aker, Soo-Zin Kim-Wanner

Hessisches Krebsregister, Hessisches Landesprüfungs- und Untersuchungsamt

im Gesundheitswesen, Frankfurt am Main, Deutschland

Background: e possible cancer risk of exposures associated with solid

waste landll sites is under continuous discussion. Reliable evidence is

sparse, as analyses require many covariates from diverse data sources and

long-term observations. e present study aimed to rst give a systematic

overview of recent research on cancer risk close to landll sites and sec-

ond to point out and compare the current research situation available for

Germany.

Methods: We conducted a literature search according to PRISMA guide-

lines by using the Medline database PubMed. Studies were included if

they reported on exposure to residents living in closer proximity to land-

ll sites and cancer risk either dened as incidence or mortality. e focus

was on publications reporting on German data. Furthermore, a review and

comparison of international studies and available data were performed.

Result: e literature search showed that very few studies have been

published including German data. One German study was found inves-

tigating on the landll site „Ihlenberg“ which reported a higher cancer

incidence for occupational exposure but not for the cohort of residents

[1]. Few studies from other countries reported higher cancer mortality,

especially lung cancer but evidence was mostly inadequate due to study

quality. Most studies were conducted 15 years ago or older, mainly in

Europe, North America or Asia.

Discussion: e present review highlighted a lack of studies regarding

the association between residency in the proximity of landll sites and

cancer risk in the German context. Due to structural dierences of landll

sites between countries, it is dicult to transfer study results from other

countries to Germany.

Conclusion: Future research should ll this gap of knowledge for

Germany.

Indication of source:

1. Stefan Weiß, Wolfgang Homann. Epidemiologische Untersuchung zu

Tumorerkrankungen in der Umgebung der Deponie Ihlenberg (2009). URL:

http://www2.medizin.uni-greifswald.de/icm/index.php?id=357 (Accessed:

30.08.2021)

Disclosure Statement: e authors declare no conict of interest.

716

Uptake of NCCN-recommended care of patients diagnosed

with leading cancer entities in Sub-Saharan Africa – a

multinational, population-based cohort study 2009-2016

Nikolaus Mezger1, Tobias Paul Seraphin1, Robert Richter1, Mirko Griesel1,

Lucia Hämmerl1, Jana Feuchter1, Yvonne Walburga Joko-Fru2,3,

Anelle Zietsman2,4, Jean-Félix Péko2,5, Nathan Buziba2,6,

MaryNyanchama2,7, Cesaltina Lorenzoni Ferreira2,8,

Eva Johanna Kantelhardt1,9

1Institute of Medical Epidemiology, Biometrics and Informatics, Martin-Luther-

University Halle-Wittenberg, Halle (Saale), Deutschland

2The African Cancer Registry Network, INCTR African Registry Programme,

Oxford, Vereinigtes Königreich

3Nueld Department of Population Health, University of Oxford, Oxford,

Vereinigtes Königreich

4Dr AB May Cancer Care Centre, Windhoek Central Hospital, Windhoek, Namibia

5Registre des cancers de Brazzaville, Brazzaville, Congo

6Eldoret Cancer Registry, Moi Teaching and Referral Hospital, Eldoret, Kenya

7Kampala Cancer Registry, Makerere University School of Medicine, Kampala,

Uganda

8Departamento de Patologia, Faculdade de medicina, Universidade Eduardo

Mondlane, Hospital Central de Maputo, Maputo, Mozambique

9Department of Gynaecology, Martin‐Luther‐University Halle‐Wittenberg, Halle

(Saale), Deutschland

Purpose: We aimed to assess uptake of care concordant with NCCN

Iium gin from ow roportion of patients Harmonized Guidelines for Sub-

Saharan Africa (SSA).

Methods: Our observational study covered 11 population-based can-

cer registries in 10 countries. Per registry, random samples diagnosed

from 2010 to 2015 with leading entities were selected: breast (BCa),

cervical, prostate (PCa), colorectal cancer and non-Hodgkin lym-

phoma (NHL). Registry data were actively updated assessing hos-

pital records. Diagnostics and cancer-directed therapy (CDT) were

evaluated for degree of concordance to the NCCN Harmonized Guidelines.

Results: Of 3251 patients, records could be “traced” for 58%. Early and

advanced disease was found in 4, metastatic in 1 of 5. HIV infection was

found in 2 of 5 tested, and ECOG PS ≥ 2 in half of all assessed. Diagnostics

relevant for CDT were missing for a considerable proportion of patients,

e.g. Gleason score for half of PCa, hormone receptor status for 4 in 5 BCa,

and subtype for 6 in 10 NHL patients. Any CDT was identied in 2 of

3 traced. In patients eligible (n=906), guideline-concordant therapy was

found in 1 of 9, with deviations in 5, and no therapy in 2 of 9. Patients with

BCa and cervical cancer, early stage, low ECOG PS and medium HDI-

origin were more likely to access guideline concordant care.

Discussion: Cancer cases in SSA will rise up to one million by 2040 annu-

ally. ough many patients presented with potentially curable disease,

access to diagnostics and treatment was low compared to hospital-based

cohorts.

Conclusion: is real-world population-based data shows the need for

timely, quality assured and aordable oncology service. Our study informs

clinicians and policy-makers on overall and entity-specic opportunities

for improvement of cancer care in SSA.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts60

862

Prevalence and Treatment of patients with dierent types of

Non-Hodgkin Lymphoma in Germany

Karina Manz1; Valeria Weber1; Dorota Pawlowska-Phelan2; Ariane Höer1;

Anja Mocek1; Tina Ploner2; Heiko Schellhorn3

1IGES Institut GmbH, Berlin, Deutschland

2InGef – Institute for Applied Health Research Berlin GmbH, Berlin, Deutschland

3Roche Pharma AG, Grenzach-Wyhlen, Deutschland

Background: Little is known about the antineoplastic treatment of chronic

lymphocytic leukemia (CLL), follicular lymphoma (FL), and diuse large

B-cell lymphoma (DLBCL) in the German real world setting. Based on

German health claims data, we estimated the prevalence of CLL, FL, and

DLBCL and described the treatment of prevalent patients.

Methods: is retrospective cohort study was based on the Institute for

Applied Health Research Berlin (InGef) research database and covered the

years 2018 to 2020. Patients were identied based on documented ICD-10

diagnosis codes (C91.1 [CLL], C82 [FL], and C83.3 [DLBCL]). e treat-

ment was described by assessing the share of patients who received at least

one pre-dened disease-related therapy (combination or monotherapy)

during the respective year. erapy lines were not dierentiated.

Result: e estimates of the prevalence in 2020 were 0.13 % (CLL), 0.05

% (FL), and 0.04 % (DLBCL). In each condition, the prevalence increased

with age until peaking in 75-84 year-olds.

In 2020, the most commonly received therapies in prevalent CLL patients

were ibrutinib, mono (8.9 %), venetoclax, mono (2.7 %), and rituximab +

bendamustine (R-Benda) (1.8 %). From 2018 to 2020, the share of patients

who received R-Benda decreased.

In 2020, the rituximab-based therapies R-Benda and R-CHOP were

received by 3.2 and 0.9 % of FL patients, respectively. 5.1 % received obinu-

tuzumab, mono and 2.4 % obinutuzumab + bendamustine (G-Benda).

From 2018 to 2020, the share of FL patients who received obinutuzumab,

mono and G-Benda increased.

In 2020, R-Benda and R-CHOP were received by 2.7 and 2.9 % of DLBCL

patients, respectively.

Discussion: Our study provides recent estimates of the prevalence of CLL,

FL, and DLBCL, and insights into the treatment situation of prevalent

patients in Germany. e results must be interpreted within the limita-

tions of German health claims data.

Conclusion: is study may serve as a starting point for future longitudi-

nal analyses describing treatment pathways.

Disclosure Statement: e authors declare no conict of interest.

876

Spatial inequalities of tumour size at diagnosis in Germany:

An ecological study in eight federal states

Philipp Jaehn1,2; Andreas Bergholz1,2; Christine Holmberg1,2

1Institute of Social Medicine and Epidemiology, Brandenburg Medical School

Theodor Fontane, Brandenburg an der Havel , Deutschland

2Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor

Fontane, Potsdam, Deutschland

Background: A place of residence with high socioeconomic deprivation,

low social capital, and a rural settlement structure is associated with an

advanced stage at cancer diagnosis in several international contexts, how-

ever, few studies have examined these characteristics in combination. We

aimed to assess the association of these spatial factors with primary tumor

size at diagnosis of selected cancer types in Germany.

Methods: All incident cases of female breast cancer, colorectal cancer,

malignant melanoma, uterine cancer, and male bladder cancer were

included. Cases were collected by epidemiological cancer registries

in eight German states between 2010 and 2014. e T-status was used

to dene an advanced tumor size at diagnosis. Sex-specic, mutually

adjusted associations of spatial characteristics with advanced tumor size

and intraclass correlation coecients (ICC) were estimated by multilevel

logistic regression at the level of administrative districts. Missing data on

tumor size were accounted for by multiple imputation.

Result: A total of 386,223 cases were included in this analysis. High spatial

socioeconomic deprivation was associated with an advanced tumor size

of colorectal cancer and malignant melanoma. For malignant melanoma,

low spatial social capital in women and men and a rural settlement struc-

ture in men were related with advanced tumor size. Meaningful ICCs were

found for malignant melanoma. No associations were identied for breast

cancer, uterine cancer, and bladder cancer.

Discussion: Limitations of this study include moderate proportions of

missing data on T-status and a high heterogeneity of regional character-

istics at the level of administrative districts. In contrast to results from

international studies, socioeconomic deprivation and rurality were not

associated with tumor size of breast cancer.

Conclusion: Spatial socioeconomic deprivation, spatial social capital, and

rurality are independent predictors of tumor size at diagnosis of malig-

nant melanoma.

Disclosure Statement: e authors declare no conict of interest.

906

WAYFIND-R: Delivering a high-quality real-world data (RWD)

global registry of patients diagnosed with a solid tumor and

proled with next-generation sequencing (NGS)

Christophe Le Tourneau1; Allan Hackshaw2; Jean-Yves Blay3; Jan Geissler4;

Clare Turnbull5; Camille Perret6; Olga Skatkova6; Martina von Meyenn6;

Rodrigo Dienstmann7

1Institut Curie, Paris cedex 05, Frankreich

2UCL Cancer Institute, London, Vereinigtes Königreich

3Centre Léon Bérard, Lyon, Frankreich

4Patvocates GmbH, Riemerling, Deutschland

5The Institute of Cancer Research , London, Vereinigtes Königreich

6F. Homann-La Roche Ltd, Basel, Schweiz

7Oncoclínicas Grupo, São Paulo, Brasilien

Background: NGS-based, molecularly guided therapy is becoming a

pivotal part of precision oncology. Rare molecular cancer subtypes pose

diculties in traditional clinical trials; collecting patient RWD can help

elucidate the eectiveness of targeted therapies, molecular tumor boards

(MTBs) and NGS-based genomic proling. WAYFIND-R (NCT04529122)

is a global registry that: 1) characterizes the treatments and clinical course

of patients with cancer; 2) provides a data research platform to evaluate

real-world treatment decisions and outcomes; 3) supports the design/con-

duct of epidemiological research and clinical trials. WAYFIND-R will pro-

vide key learnings on data quality, sharing, and privacy for contemporary

disease registries.

Methods: WAYFIND-R is a prospective registry with longitudinal,and

standardized data collection to enhance data quality and minimize miss-

ing data. WAYFIND-R includes adults with any type/stage of solid tumor

proled with NGS. NGS details, patient sociodemographics, cancer char-

acteristics, patient-relevant safety data, treatment decisions, and outcomes

are collected at baseline and prospectively every ≤6 months. By 2026,

WAYFIND-R aims to enroll ~15,000 patients in ≥35 countries.

Result: As of April 2022 154 patients have been enrolled.

Discussion: A key component is the potential to explore global and

local data within a secure analytics platform, accessed through a visual

dashboard to nd treatment decisions for similar patients elsewhere.

Researchers can access the patient-level dataset for correlative analyses,

aer independent data access committee approval. WAYFIND-R’s meth-

odological/operational aspects were guided by external experts and the

European Medicines Agency.

Conclusion: WAYFIND-R will inform on best practice for NGS-based

treatment decisions by clinicians, foster global collaborations between

cancer centers , aid understanding of disparities in patients’ access to

advanced diagnostics and therapies, and ultimately drive advances in pre-

cision oncology.

Pres. by AACR 2022

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 61

916

Conceptualization of core clinico-molecular variables for

registries enrolling patients diagnosed with a solid tumor and

proled with next-generation sequencing (NGS)

Rodrigo Dienstmann1; Clare Turnbull2; Allan Hackshaw3; Jean-Yves Blay4;

Maud Kamal5; Nicolas Servant5; Jan Geissler6; David Tamborero7;

Janick Weberpals8; Simon Fear8; Camille Perret8; Laura Perez8,

Martina von Meyenn8; Christophe Le Tourneau5

1Oncoclínicas Grupo, São Paulo, Brasilien

2The Institute of Cancer Research , London, Vereinigtes Königreich

3UCL Cancer Institute, London, Vereinigtes Königreich

4Centre Léon Bérard, Lyon, Frankreich

5Institut Curie, Paris, Frankreich

6Patvocates GmbH, Riemerling, Deutschland

7Karolinska Institutet , Stockholm, Schweden

8F. Homann-La Roche Ltd, Basel, Schweiz

Background: In precision oncology, tailored treatment decisions are

largely driven by genomic alterations in a patient’s tumor. To support

epidemiological research we initiated a registry that enrolls patients diag-

nosed with a solid tumor and proled with NGS. Collecting and stan-

dardizing variables of interest across the patient journey is critical for

data harmonization and understanding clinical relevance. We propose

a framework for identifying core variables most critical for solid tumor-

based, real-world data studies and registries in precision oncology.

Methods: A patient representative and panel of experts in oncology, epi-

demiology, bioinformatics and molecular pathology was assembled to

compile a dra variables list. To reduce the burden of data collection and

missingness, the variables were categorized by decreasing importance and

reconciled with dra European Medicines Agency guidelines on regis-

try-based studies. If applicable internationally harmonized coding dictio-

naries were used to standardize the variables.

Result: e dra list comprised ~500 variables and was reconciled to

~150; highest priority was given to patient information, NGS test results

(e.g. actionable alterations, genomic signatures), cancer details (e.g.

disease ontology, staging, metastases), and therapy details/outcomes.

Variables with moderate to lower priority comprised NGS (e.g. technical,

quality criteria), familial cancer history, adherence to molecular tumor

board recommendations, and primary cause of death.

Discussion:e variable list was created to: describe a patient’s cancer his-

tory and journey eectively; allow conduct of comparative eectiveness

studies and comparisons with clinical trials; and represent key risk factors

or important confounders for prognosis or statistical analysis adjustments.

Conclusion: is list provides viable guidance for conducting research-

and regulatory-grade real-world data-based precision oncology studies,

and facilitating standardized data collection and thus pooling from var-

ious datasets.

Pres at AACR 2022

Disclosure Statement: e authors declare the following: Advisory Board: BMS,

Roche, Sano-Aventis, GSK, Novartis, Pierre Fabre, Guardant Health

970

Overall and country-specic agreement in symptom

reporting between prostate cancer patients and healthcare

professionals in the international multicentre REQUITE study

Philipp Heumann1,2; Irmgard Helmbold1; David Azria3; Erik Briers4;

Ananya Choudhury5; Dirk De Ruysscher6,7; Marie-Pierre Farcy-Jacquet8;

Tiziana Rancati9; Barry Rosenstein10; Elena Sperk11; Christopher Talbot12;

Ana Vega13; LIV Veldeman14; Tim Ward15,16; Adam Webb12;

Catharine West17; Jenny Chang-Claude1,18

1German Cancer Research Center (DKFZ), Heidelberg, Deutschland

2Johannes Gutenberg University Mainz, Mainz, Deutschland

3Montpellier Cancer Institute, Montpellier, Frankreich

4Patient advocate, Hasselt, Belgien

5Christie Hospital, University of Manchester, Manchester, Vereinigtes Königreich

6Maastro Clinic, Maastricht, Niederlande

7KU Leuven, Leuven, Belgien

8CHU Nimes, Nimes, Frankreich

9Istituto Nazionale dei Tumori, Milan, Italien

10Icahn School of Medicine at Mount Sinai, New York, USA

11Medical Faculty Mannheim, University of Heidelberg, Mannheim, Deutschland

12University of Leicester, Leicester, Vereinigtes Königreich

13Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela,

Spanien

14Ghent University Hospital, Ghent, Belgien

15Trustee Pelvic Radiation Disease Association, Vereinigtes Königreich

16NCRI CTRad Consumer, Vereinigtes Königreich

17University of Manchester, Manchester, Vereinigtes Königreich

18University Cancer Center Hamburg, University Medical Center

Hamburg-Eppendorf, Hamburg, Deutschland

Background: Previous studies showed that healthcare professionals and

patients had only moderate to low agreement on their assessment of treat-

ment-related symptoms. Here we aimed to determine the levels of agree-

ment in a large cohort of prostate cancer patients.

Methods: Analyses were made of data from 1756 prostate cancer patients

in seven European countries and the USA treated with external beam

radiotherapy (RT) and/or brachytherapy and recruited into the pro-

spective multicentre cohort REQUITE study (www.requite.eu). Eleven

pelvic symptoms at the end of RT were compared aer translating patient-

reported outcomes (PROs) into CTCAE based healthcare professional

ratings. Gwet’s AC2 agreement coecient was calculated across countries

and country-specically for each symptom. To compare severity of grad-

ing between patients and healthcare professionals, percent agreement and

deviations for each symptom were examined.

Result: Across countries, agreement was very good (haematuria, rectal

bleeding, management of sphincter control) or good (diarrhoea, erectile

dysfunction, urinary incontinence) for 6 of 11 symptoms. Libido/ orgasmic

dysfunction and urinary retention showed moderate whereas urinary fre-

quency fair, proctitis and urinary urgency poor agreement. More observ-

able symptoms with few symptomatic patients such as haematuria and

rectal bleeding showed little between-country variation in agreement.

For subjective symptoms such as proctitis, considerable dierences were

observed between countries, ranging from poor to good agreement.

Discussion: Agreement was better for more observable than subjec-

tive symptoms, with patients tending to grade their symptoms more

severely. Between-country dierences in levels of agreement varied across

symptoms

Conclusion: PROs should complement symptom assessment by health-

care professionals and be taken into consideration for clinical decision-

making to incorporate the patient perspective. Parts of this analysis were

presented at the 2022 Congress of the German Society for Epidemiology.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts62

Gastrointestinal (Colorectal) Cancer

Best-of-Abstract-Vortrag

583

PFKFB3 inhibition by 3PO as a therapeutic target in colorectal

cancer

Marcus Edelmann1; Shuang Fan1; Tina Goldhardt1; Karly Conrads2;

TimBeissbarth2; Stefan Rieken3; Michael Ghadimi1; Tiago De Oliveira1;

Lena-Christin Conradi1

1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und

Kinderchirurgie, Göttingen, Deutschland

2Universitätsmedizin Göttingen, Institut für Medizinische Bioinformatik ,

Göttingen, Deutschland

3Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,

Göttingen, Deutschland

Background: Patients with rectal cancer in UICC stage II/III may

undergo neoadjuvant chemoradiotherapy (CRT). However, resistance

is a major clinically observed obstacle. Abnormal neoangiogenesis and

increased glucose metabolism are characteristics of cancer. In particular,

the bifunctional enzyme PFKFB3 represents a promising target. PFKFB3,

as an indirect stimulator of glycolysis, aects the glycolytic activity of

cancer cells and was shown to induce tumor vessel normalization upon

inhibiton. Moreover, high PFKFB3 expression was shown to be associated

with poor prognosis for patients with CRC. is highlights PFKFB3 as an

attractive therapeutic target.

Methods: We assessed the eect of PFKFB3 inhibition by 2E-3-(3-

pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) in CRC cell lines on

cell viability, cell death as well as invasion and migration ability. To verify

a potential radiosensitizing eect of 3PO a colony formation assay was

performed. Subsequently, in vivo studies were performed to evaluate the

TVN eect of combined therapy of 3PO and (C)RT in patient-derived

xenogras tumors.

Result: Our in vitro ndings showed that 3PO treatment of CRC cells

aects cell proliferation and viability in a concentration-dependent man-

ner and reduces CRC cell invasion and migration. In addition, we found

a radiosensitizing eect on CRC cells. Moreover, our results demonstrate

that inhibition of PFKFB3 induces TVN and alleviates tumor hypoxia

culminating in increased tumor necrosis upon combined therapy of 3PO

with (C)RT in vivo.

Discussion: Increased glycolysis and tumor hypoxia are thought to

induce resistance to radiotherapy in various tumors. We hypothesize that

RT resistance may be overcome by inducing TVN. A potential target is

PFKFB3, a crucial regulator of glycolysis. Here, we provide a rst insight

into the response of CRC cells to 3PO.

Conclusion: Finally, our in vitro and in vivo results support 3PO as a

potential future treatment complement for rectal cancer patients.

Disclosure Statement: e authors declare no conict of interest.

Poster

NOTCH Activation via gp130/STAT3 Signaling Confers

Resistance to Chemoradiotherapy

Melanie Spitzner1; Kristin Koerdel2; Thomas Meyer3; Niklas Engels2;

Florian Krause1; Jochen Gaedcke1; Lena-Christin Conradi1; Martin

Haubrock4; Tim Beißbarth5; Andreas Leha6; Steven A. Johnsen7;

B. Michael Ghadimi8; Stefan Rose-John9; Jürgen Wienands10;

Marian Grade8

1University Medical Center Goettingen, Department of General, Visceral and

Pediatric Surgery, Göttingen, Deutschland

2University Medical Center Goettingen, Institute of Cellular and Molecular

Immunology, Göttingen, Deutschland

3University Medical Center Goettingen, Department of Psychosomatic Medicine

and Psychotherapy, German Centre for Cardiovascular Research, Göttingen,

Deutschland

4University Medical Center Goettingen, Institute of Medical Bioinformatics,

Göttingen, Deutschland

5University Medical Center Goettingen, Institute of Medical Bioinformatics,

Goettingen, Deutschland

6University Medical Center Goettingen, Department of Medical Statistics,

Göttingen, Deutschland

7Mayo Clinic, Division of Gastroenterology and Hepatology, Gene Regulatory

Mechanisms and Molecular Epigenetics Laboratory, Rochester, USA

8University Medical Center Goettingen, Department of General, Visceral and

Pediatric Surgery, Goettingen, Deutschland

9Christian-Albrechts-University, Institute of Biochemistry, Kiel, Deutschland

10University Medical Center Goettingen, Institute of Cellular and Molecular

Immunology, Goettingen, Deutschland

Background: For locally advanced rectal cancer, the treatment concept

includes a preoperative chemoradiotherapy (CRT), followed by radical

surgical resection of the tumor. Unfortunately, the response to CRT varies

tremendously among patients, and about one third will have only little or

no response to the preoperative treatment. erefore, resistance of tumor

cells to CRT represents a fundamental problem in clinical oncology. e

underlying molecular mechanisms remain complex and have not yet been

suciently claried.

Methods: Blocking inammatory cytokine receptor signaling on response

to CRT was assessed in colorectal and esophageal cancer cell lines, com-

plemented by in vivo experiments using a rectal cancer xenogra mouse

model with fractionated CRT. Mutational analyses of STAT3 and studies

in the absence or presence of cytokine receptor activation were performed

to assess the requirement of active STAT3 signaling. To delineate how

inammatory signals control CRT resistance, global transcriptional activ-

ity was assessed using RNA sequencing.

Result: Here we show that blocking inammatory cytokine receptor

signaling via STAT3 re-sensitized treatment-refractory cancer cells and

abolished tumor growth in vivo when applied together with CRT. STAT3

executed treatment resistance by triggering the expression of RBPJ, the

key transcriptional regulator of the NOTCH pathway. e mandatory

RBPJ interaction partner, NOTCH intracellular domain, was provided

by tumor cell-intrinsic expression of NOTCH ligands that caused tonic

NOTCH proteolysis. In fact, NOTCH inhibition phenocopied the eect

of blocking STAT3 signaling. Moreover, genetic proling of rectal cancer

patients revealed the importance of the STAT3/NOTCH axis as NOTCH

expression correlated with clinical outcome.

Discussion and Conclusions: Our data uncovered an unprecedented

signal alliance between inammation and cellular development that

orchestrated resistance to CRT. Clinically, our ndings allow for biomark-

er-driven patient stratication and oer novel treatment options.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 63

103

Encorafenib and cetuximab in patients with metastatic,

BRAF V600E-mutated, colorectal carcinoma: a multi-centric,

multi-national, prospective, non-interventional study

inGermany, Austria and Switzerland – BERING CRC

Gerald Prager1; Gerdt Hübner2; Jan Schröder3; Helmut Forstbauer4;

Jens Kisro5; Manfred Welslau6; Dieter Bürkle7; Eyck von der Heyde8;

Harald Müller-Huesmann9; Beate Krammer-Steiner10; Christiane

Hering-Schubert11; Ulrich Popper12; Armin Gerger13; Richard Greil14;

Frank Reichenbach15; Dirk Arnold16; Ralph Fritsch17; Susanna Hegewisch-

Becker18; Arndt Vogel19; Anna Dorothea Wagner20; Thomas Winder21;

Dieter Koeberle22,23; Sebastian Stintzing24

1Department of Medicine I, Medical University Vienna, Vienna, Österreich

2oho - practice for oncology, Oldenburg i.H., Deutschland

3Oncological Practice Mülheim, Mülheim, Deutschland

4Practice Network Troisdorf, Troisdorf, Deutschland

5Oncological Practice Lübeck, Lübeck, Deutschland

6Oncological Practice Aschaenburg, Aschaenburg, Deutschland

7Oncological Practice Schorndorf, Schorndorf, Deutschland

8Oncological Practice Hannover, Hannover, Deutschland

9St. Josef Hospital Paderborn, Paderborn, Deutschland

10Department of Hematology and Oncology, Rostock South City Medical Center,

Rostock, Deutschland

11St. Georg Hospital Eisenach, Eisenach, Deutschland

12Department of Internal Medicine I for Hematology with Stem Cell

Transplantation, Hemostase-ology and Medical Oncology, Ordensklinikum Linz,

Linz, Österreich

13Division of Clinical Oncology, Medical University Graz, Graz, Österreich

14Paracelsus Medical University Salzburg, Salzburg Cancer Research Institute-

CCCIT and Cancer Cluster Salzburg, Salzburg, Österreich

15Pierre Fabre Pharma GmbH, Freiburg, Deutschland

16Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Deutschland

17Klinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich,

Zürich, Schweiz

18HOPE-Practice for Oncology Hamburg, Hamburg, Deutschland

19Hannover Medical School, Hannover, Deutschland

20Department of Oncology, Lausanne University Hospital and University of

Lausanne, Lausanne, Schweiz

21Internal Medicine II, Landeskrankenhaus Feldkirch, Feldkirch, Österreich

22Tumorzentrum, Claraspital Basel, Basel, Schweiz

23University Bern, Bern, Schweiz

24Department of Hematology, Oncology, and Cancer Immunology (CCM),

Charité - Universitaetsmedizin Berlin, Berlin, Deutschland

Background: Targeted treatment with encorafenib plus cetux-

imab represents a new standard of care for patients with BRAF

V600E-mutant metastatic colorectal cancer upon systemic therapy.

is combination has been approved in the EU and Switzerland in 2020.

e approval was based on the data from the BEACON CRC trial; the

updated analysis showed a median overall survival (mOS) of 9.3 months

for the treatment with encorafenib plus cetuximab compared to a mOS of

5.9 months with chemotherapy plus cetuximab (hazard ratio [HR], 0.61

[95% CI, 0.48 to 0.77]) and an objective response rate of 20% compared to

2%. e tolerability prole was consistent with the known safety prole.

As data from controlled clinical trials are based on a selected patient pop-

ulation, the non-interventional study (NIS) BERING CRC investigates

the use of encorafenib plus cetuximab under real-world conditions in a

broader patient population.

Methods: BERING CRC is an ongoing multi-national, multi-centric,

prospective, longitudinal NIS. It is the rst NIS to investigate the real-

world use of encorafenib plus cetuximab in BRAF V600E-mutant met-

astatic colorectal cancer upon systemic treatment in Germany, Austria

and Switzerland. e study aims to enroll 500 patients from 96 German,

Austrian and Swiss sites within an expected enrollment period of 6

yrs.e study observes patients treated according to the approval as given

in the respective Summary of Product Characteristics. e primary objec-

tive is to assess the 1-year OS rate. Secondary endpoints include ecacy,

quality of life, safety and tolerability of encorafenib plus cetuximab. e

inuence of prognostic factors on ecacy, as well as safety and tolerability

will also be assessed.

Result: From Sep 2020 to Apr 2022, 81 patients have been included from

80 open sites.

Discussion: Based on the initial 100 patients enrolled, a rst interim

analysis will be performed.

Conclusion: e study design and current enrollment status will be

presented.

Indication of source:

1 Koeberle D. et al., DGHO congress 2021, abstract #75

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

165

Forschungspartnerschaft Darmkrebs (Prioritiy Setting

Partnership Colorectal Cancer)– Identifying and prioritizing

unanswered questions about colorectal cancer

Magdalena Holze1; Rosa Klotz1; Colette Dörr-Harim2; Azaz Ahmed3;

André Mihaljevic2

1Chirurgische Klinik, Heidelberg, Deutschland

2Uniklinik Ulm Abt Chirurgie, Ulm, Deutschland

3Nationales Centrum fu¨r Tumorerkrankungen – NCT, Heidelberg, Deutschland

Background: Colorectal cancer (CRC) is the third most common can-

cer worldwide and the second and third leading cause of cancer death

in women and men. With improving therapeutic options, the number of

elderly people living with CRC increases.

Research projects are currently driven by scientists or pharmaceuti-

cal industry whereas other stakeholders like patients, carers, physi-

cians etc. are rarely involved. Accordingly, it remains unclear which

research questions should be answered with high priority. To address

this mismatch, the “Priority Setting Partnership Colorectal Cancer”

(Forschungspartnerscha Darmkrebs (FP)) was initiated. e FP brings

patients, carers, clinicians and other relevant stakeholders together to

identify and prioritize the most important unanswered questions about

diagnostics, therapy and oncological aercare of CRC with an emphasis

on special needs of elderly patients.

Methods: Supported by the UK-based James Lind Alliance the FP is per-

formed by the following method ensuring transparency of the process and

balanced inclusion of all stakeholders’ interests and perspectives. Aer

creating a Steering Group, 1108 questions were gathered via a nationwide

survey. Responses were summarized, categorized and a systematic litera-

ture search was performed to check against current evidence. In a second

survey, interim priority setting was carried out. In September 2021, in the

nal consensus workshop the TOP 10 list of research priorities will be

identied which will be published and promoted to initiate relevant future

projects.

Result: At the congress the nal results of the TOP 10 list will be presented.

Discussion: Priorities identied in the FP CRC provide an important

basis for future research to initiate patient-centered research and funding.

Conclusion: e introduced FP is the rst nationwide project with this

new approach of patient involvement bringing together all stakeholders in

CRC in prioritizing future research.

Disclosure Statement: e authors declare no conict of interest.

170

Methylated septin 9 as a progression parameter in colorectal

cancer compared to CEA and CA19-9

Laura Schulz1; Sabine Leerho1; Ernst W. Kolbe1; Arnold M. Raem1;

Günther Winde1

1Medizin Campus Ostwestfalen der RUB, Klinikum Herford, Universitätsklinik

für Allgemein- und Viszeralchirurgie, Thoraxchirurgie und Proktologie, Herford,

Deutschland

Purpose: To improve the prognosis of patients suering from colorectal

cancer, reliable follow-up is crucial. So far, CEA and CA19-9 are used for

routine monitoring, despite their limited sensitivity. erefore, detecting

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts64

circulating tumour cells or tumour DNA in plasma could be of greater

value, e.g. the use of “methylated Septin 9” for “liquid biopsy”. In this

study mSEPT9 was investigated as a possible progression parameter in

colorectal cancer and compared to the common tumour markers.

Methods: DKG-accredited (ST-D469), prospective single center study,

n = 122, m/f patients from Herford University Dept. of Surgery with col-

orectal cancer UICC stage I-IV, curative intention to treat. Blood sam-

pling: preoperatively and postoperatively at 1/ 6/ 12 weeks tested for

mSEPT9, CEA and CA19-9 using Epi-proColon® 2.0 test and ECLIA.

e results have been validated by the relative amount of extracted DNA

(ACTB), the use of control samples and by reaching the dened crossing

point value (CP) < 40.5 for all PCR control replicates. 2/3 positiv PCR

replicates indicated a Septin9-positive result. Results were analysed using

GraphPad Prism™.

Results: Preoperatively, mSEPT9 appeared more sensitive (52%) than

CEA (31%) and CA19-9 (14%). 3 months postoperatively, the patholog-

ical test results reduced for mSEPT9 (25%) and CEA (23%), but not for

CA19-9 20%. e highest sensitivity was achieved by mSEPT9 in stage

UICC IV (94%) and T4 (87%) or tumour localisation in the colon (53%;

rectum 51%). mSEPT9 indicated metastases (sensitivity 83%) and resid-

ual tumour (R1: 50%; R2:100%).

Discussion: So far, mSeptin 9 has only been investigated as a screening

parameter. Studies from Devos et al. (2009) and Ørnto et al. (2015)

demonstrated the high specicity (82-95%) and a low false positive rate of

the Epi-proColon® 2.0 CE test (4-5%).

Conclusion: Our results show the benecial use of mSeptin9 as a potent

follow-up parameter of colorectal cancer especially for R+ status patients.

A prospective comparison of the R+ patients with PET-CT-results is

planned.

Disclosure Statement: e authors declare no conict of interest.

245

RAS mutant metastatic colorectal cancer – Real-world data

from more than 1000 patients from the Clinical Tumor

Registry Colorectal Cancer (TKK)

Steen Dörfel1; Christiane Bernhardt2; Egbert Eggers3; Stefan Fruehauf4;

Christoph Maintz5; Joachim Behringer6; Anna Hof7; Natalie Wetzel7;

Lisa Kruggel7; Karin Pottho7

1Onkozentrum Dresden/Freiberg, Dresden, Deutschland

2Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Deutschland

3Kreiskrankenhaus Torgau Innere Medizin Darmzentrum, Torgau, Deutschland

4Klinik Dr. Hancken Hämatologie und Onkologie, Stade, Deutschland

5MVZ West GmbH Würselen Hämatologie-Onkologie, Würselen, Deutschland

6Onkologische Schwerpunktpraxis Speyer, Speyer, Deutschland

7iOMEDICO, Freiburg, Deutschland

Background: For patients (pts) with RAS mutant (mut) metastatic col-

orectal cancer (mCRC) the therapeutic benet derived from established

treatment regimens is still unclear. Guidelines recommend chemotherapy

(CT; uoropyrimidine, irinotecan, oxaliplatin) with/without anti-angio-

genic agents for two treatment lines. ere is no established standard of

care for subsequent treatment lines. Real-world data on pts with RAS mut

mCRC are scarce.

Methods: Since 2006, the Tumor Registry Colorectal Cancer (TKK) pro-

spectively collects data on patient and tumor characteristics, treatment,

outcome, and quality of life of CRC pts in routine practice in Germany.

e treating physicians decide treatments as per clinical routine and inde-

pendently from the registry. Here we analyze patient and tumor charac-

teristics, longitudinal treatment details and outcome of 1087 pts with (K)

RAS mut mCRC from begin of palliative rst-line therapy.

Result: Between 2010 and 2018, 1087 pts with (K)RAS mut mCRC were

enrolled. Median age of pts was 68 years. Since 2010, KRAS testing could

be documented. Since 2014 details on extended RAS mutation status test-

ing (exons 2/3/4 for KRAS or NRAS) were documented (n=897).

Pts with (K)RAS mut mCRC were mostly treated with FOLFIRI+BEV

(30%), FOLFOX+BEV (25%), FOLFOX (13%) and FOLFIRI (9%).

No major changes were seen in choice of treatment over time. 747 pts

(69%) received 2nd-line therapy, of those 18% of pts were treated with

FOLFIRI+BEV followed by FOLFOX+BEV (16%). 439 pts (40%) received

3rd-line therapy, of those 12% of pts received FOLFIRI+BEV. e percent-

age of pts receiving 3rd-line triuridine/tipiracil increased from 9% in

2016 to 38% in 2019.

Median overall survival for all evaluable pts with (K)RAS mut mCRC was

21.9 months (62% events, 95%-CI: 20.9 - 23.0 months). Updated data will

be presented.

Conclusion: is analysis of the RAS mut mCRC population enrolled

prospectively in the TKK database provides important insights into treat-

ment patterns, sequential treatments, and outcome of patients with RAS

mut mCRC in routine clinical practice in Germany.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

276

Survival of patients (pts) with BRAF V600E mutated metastatic

colorectal cancer (mCRC) treated with systemic therapy in a

real-world setting

Moritz Götz1,2,3; Stefan Kasper2,3,4; Andreas Paul2,3,5; Peter Markus6;

Brigitte Schumacher7; David Albers7; Vivian Rosery2,4; Katharina Laue2,4;

Gregor Zaun2,4; Karina Kostbade2,4; Michael Pogorzelski2,4;

Kurt Werner Schmid1,2,3; Hans-Ulrich Schildhaus1,2,3; Marcel Wiesweg2,3,4;

Martin Schuler2,3,4; Isabel Virchow2,4

1West German Cancer Center, University Hospital Essen, Institute of Pathology,

Essen, Deutschland

2Medical Faculty University Duisburg-Essen, Essen, Deutschland

3German Cancer Consortium (DKTK), Partner site University Hospital Essen,

Essen, Deutschland

4West German Cancer Center, University Hospital Essen, Department of Medical

Oncology, Essen, Deutschland

5West German Cancer Center, University Hospital Essen, Department of General,

Visceral and Transplant Surgery, Essen, Deutschland

6Elisabeth Hospital Essen, Department of General Surgery and Traumatology,

Essen, Deutschland

7Elisabeth Hospital Essen, Department of Gastroenterology, Essen, Deutschland

Background: Pts with BRAF mutated mCRC have a dismal prognosis

with median overall survival (OS) times of only 1.5 years in clinical trials.

Current guidelines recommend intensive 1st-line chemotherapy (CTX)

with FOLFOXIRI, and 2nd line with a BRAF inhibitor (BRAFi) in combi-

nation with EGFR antibodies. However, in real-world, a substantial num-

ber of pts do not qualify for intensive CTX. e best therapeutic strategies

in these pts remain elusive. Here, we present data from BRAF mutated

mCRC pts treated at a large German comprehensive cancer centre.

Methods: is is a retrospective single-center analysis. Clinico-

pathological data and treatments were extracted from the electronical

health record. Progression free-survival (PFS) was dened from start of

CTX to progress or death, OS was dened from start of palliative CTX

until death, pts were censored at time point of last follow up. Type of CTX

was correlated with PFS and OS.

Result: In total, 51 evaluable pts were identied. Median age was 62.2

years, and 58.9% were female. In 71.4% of pts, primary tumour was right-

sided, and 26.1% had a dMMR status. Palliative CTX was administered

to 48 pts, while 3 pts only received BSC. Pts received 2 treatment lines in

median (range 0-5). FOLFOXIRI was administered to 12 pts (23.5%), 19

pts received FOLFOX/CAPOX, and 10 pts received FOLFIRI. A monoclo-

nal antibody (moABX) was added in 31 pts, mainly bevacizumab. Median

PFS was 8.4 months (mo) and median OS was 17.6 mo. Interestingly,

FOLFOXIRI was associated with a signicant prolonged PFS (HR 0.325;

p=0.026) but had no signicant impact on OS (HR 0.742: p=0.433). In

contrast, the use of moABX in 1st-line was associated with prolonged OS

(HR 0.523; p=0.043). In further lines, 17 pts received a BRAFi. ese pts

had a numerical longer OS of 25.1 mo compared to pts without BRAFi

therapy (13.1 mo).

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 65

Conclusion: In a real-world setting, comparable survival times could be

achieved in pts with BRAF mutated mCRC as in recently published trials.

Intensive 1st-line therapy has no impact on OS. e implementation of

moABX and BRAFi during therapy correlates with prolonged OS.

Disclosure Statement: e authors declare the following: Merck, Amgen, Roche,

Sano, Aventis, Servier, Lilly

311

Epidemiology and prognostic risk factors of appendiceal

neoplasia histological subtypes

Kathrin Halfter; Anne Schlesinger-Raab; Gabriele Schubert-Fritschle;

Jutta Engel

Institute for Medical Information Processing, Biometry and Epidemiology (IBE),

Ludwig-Maximilians-University (LMU), Munich Cancer Registry (MCR), München,

Deutschland

Purpose: Appendiceal neoplasia are a rare subtype of colorectal tumors,

the few available studies are mostly based on SEER data and lack infor-

mation on mucinous neoplasia. e aim of this retrospective registry

study was to assess epidemiology and prognosis in a European popula-

tion-based cohort of eected patients.

Methods: e nal analyses included 1 097 patients from the Munich

Cancer Registry (MCR) diagnosed between 1998 and 2020. Cases were

grouped according to tumor histology into adenocarcinoma (ADENO),

neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine car-

cinoma (MANEC), and mucinous neoplasia (LAMN and HAMN).

Joinpoint trend analysis and baseline demographic comparisons were

conducted, in addition to survival analyses using competing risk and uni-

variate/multivariate methods.

Result: Until 2016 the number of cases increased signicantly (APC =

6.86, p < .001) followed by a decline in the following years (APC = -14.82,

p = .014; average APC = 2.5, p = .046).

In univariate analysis patients with NEN (48.4%) and mucinous neo-

plasms (11.6%) fared compariably better than ADENO (36.0%) and

MANEC (3.0%, p < .0001).

A multivariate analysis revealed further histological classication was not

prognostically relevant, while older age and UICC III/IV at diagnosis were

associated with a lower prognosis. In the ADENO subgroup a high tumor

grading and a less extensive surgical tumor resection procedure were also

associated with poorer survival.

Conclusion: e previously observed increase in cases appears to be

abating, potentially due to fewer appendicitis and/or appendectomies.

Appendiceal neoplasia are histologically heterogeneous, however this

diversity becomes less relevant compared to the marked dierence to can-

cers of the remaining colon.

Disclosure Statement: e authors declare no conict of interest.

345

Case of a patient with response to combined immune

checkpoint inhibition after progression on pembrolizumab

Carolin Krekeler1; Georg Evers1; Kerstin Menck1; Andrea Kerkho1;

Wolfgang Hartmann2; Andreas Pascher3; Georg Lenz1; Micha Peeck1,4;

Annalen Bleckmann1,4

1Dept. of Medicine A - Hematology, Hemostaseology, Oncology and

Pneumology , University Hospital Münster, Münster, Deutschland

2Dept. of Pathology, University Hospital Münster, Münster , Deutschland

3Dept. of General, Visceral and Transplant Surgery, University Hospital Münster,

Münster, Deutschland

4Authors contributed equally

Background: Metastatic colorectal cancer (mCRC) with high frequency

of microsatellite instability (MSI-H) responds poorly to cytotoxic ther-

apy. e underlying mismatch repair deciency leads to the creation of

neoantigens and thus immunogenic epitopes. Treatment with immune

checkpoint inhibitors (ICI) shows ecacy and long-term response in a

proportion of mCRC patients. Single-agent ICI is the current standard of

care. Nevertheless, some patients with initial response to single-agent ICI

eventually develop progressive disease. ere are no generally accepted

recommendations regarding treatment in this situation.

Methods: We present a scientic report on the clinical course of a patient

with MSI-H mCRC treated with the combination of nivolumab (3 mg/kg)

and ipilimumab (1 mg/kg) every 3 weeks aer image-conrmed progres-

sion on pembrolizumab.

Result: A 64-year old male patient with hepatic, bone, port site and sub-

cutaneous metastases received nivolumab and ipilimumab aer tumor

progression on pembrolizumab. Aer two cycles a clinical response with

a shrinkage of the palpable subcutaneous metastases was observed. Aer

three cycles of combined ICI therapy, PET-CT revealed a partial response

with a complete metabolic remission of the bone lesion and regression

of all other metastases. Moreover, CEA and CA 19-9 levels declined and

normalized while the clinical performance status improved. e patient

tolerated the treatment well, except for pain one week aer the application

of ICI, which was controlled by oral opioids. Aer 4 cycles of combined

ICI the patient is continuing single-agent nivolumab.

Discussion: ICI are able to provide durable responses in MSI-H mCRC.

erefore, testing for MSI is required. In the case of progression on sin-

gle agent anti-PD-1 blockade, the addition of an anti-CTLA-4 drug might

help to overcome an acquired resistance to ICI monotherapy.

Conclusion: Further clinical trials are needed in order to verify the e-

cacy and safety of combined immunotherapy aer progression on single

agent ICI.

Disclosure Statement: e authors declare no conict of interest.

379

Colorectal cancer risk: the interplay of polygenic risk,

high-impact monogenic variants, and family history

Emadeldin Hassanin1; Dheeraj Bobbili2; Rana Aldisi1; Friederike David3;

Hannah Klinkhammer1,4; Nuria Dueñas5,6; Andreas Mayr4; Markus

Nöthen3; Robert Hüneburg7,8; Andreas Forstner3,9,10; Isabel Spier3,8;

Patrick May2; Peter Krawitz1; Carlo Maj1; Stefan Aretz3,8

1Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn,

Bonn, Deutschland

2Luxembourg Centre for Systems Biomedicine, University of Luxembourg,

Esch-sur-Alzette, Luxemburg

3Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn,

Deutschland

4Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty,

University Bonn, Bonn, Deutschland

5Catalan Institute of Oncology-IDIBELL, ONCOBELL, Hospitalet de Llobregat,

Barcelona, Spanien

6Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto

Salud Carlos III, Madrid, Spanien

7Department of Internal Medicine I, University Hospital Bonn, Bonn,

Deutschland

8National Center for Hereditary Tumor Syndromes, University Hospital Bonn,

Bonn, Deutschland

9Centre for Human Genetics, University of Marburg, Marburg, Deutschland

10Institute of Neuroscience and Medicine (INM-1), Research Center Ju¨lich, Jülich,

Deutschland

Background: Common, low penetrant genetic risk variants (SNPs) asso-

ciated with colorectal cancer (CRC) are distributed in the population.

Summarised in quantitative polygenic risk scores (PRS), the combined

eect might explain a substantial fraction of CRC risk variability and can

identify individuals at several times lower and greater CRC risk than the

general population. e study aims to investigate to which extent PRS,

high-impact monogenic variants for hereditary CRC (Lynch syndrome,

polyposis), and family history aect CRC risk by assessing cancer prev-

alence and cancer cumulative lifetime incidence using European popula-

tion-based data.

Methods: 163,516 individuals from the UK Biobank were stratied as fol-

lows: 1. carriers or non-carriers of rare, pathogenic germline variants in

CRC susceptibility genes, 2. individuals with low (<10%), intermediate

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts66

(10-90%) or high (>90%) PRS, and 3. individuals with or without a fam-

ily history of CRC. Multivariable logistic regression was used to compare

the odds ratio (OR) across the dierent groups while Cox proportional

hazards models were used to compute the cumulative lifetime incidence.

Result: Taking non-carriers with intermediate PRS as reference, CRC

cumulative lifetime incidence by age 78 years for carriers of monogenic

variants with low PRS is 22% and reaches 66% for carriers with high PRS,

compared to 7% and 31% for non-carriers, respectively. A suspicious fam-

ily history is associated with a further increase of the cumulative incidence

reaching 75% for carriers and 35% for non-carriers.

Discussion: e ndings demonstrate that CRC risk is strongly inu-

enced by the PRS for both a sporadic and hereditary background. A high

PRS in non-carriers confers a CRC risk comparable to monogenic vari-

ants. Family history, monogenic variants, and PRS contribute additively

to CRC risk.

Conclusion: e implementation of PRS in routine patient care will likely

improve individualised risk stratication for sporadic and hereditary

CRC, which will in turn guide tailored preventive strategies in high, mod-

erate, and low risk groups.

Disclosure Statement: e authors declare no conict of interest.

515

Eectiveness of care in German cancer centres – evidence

from the WiZen study

Veronika Bierbaum1; Martin Rößler1; Bobeth Christoph1; Michael Gerken2;

Kees Kleihues-van Tol2; Patrik Dröge3; Andreas Kloess3; Christian Günster3;

Monika Klinkhammer-Schalke2,4; Olaf Schoer1; Jochen Schmitt1

1Universitätsklinikum Carl Gustav Carus Dresden, Zentrum für Evidenzbasierte

Gesundheitsversorgung (ZEGV), Dresden, Deutschland

2Tumorzentrum Regensburg, Regensburg, Deutschland

3Wissenschaftlichs Institut der AOK (WIdO), Berlin, Deutschland

4Arbeitsgemeinschaft Deutscher Tumorzentren e.V., Berlin, Deutschland

Background: Treatment of cancer patients in certied cancer centers is

a national health care goal in Germany. While previous studies provide

some evidence that treatment in cancer centers certied by the German

Cancer Society (GCS) is associated with better patient outcomes, there

is a lack of comprehensive analysis across large populations. e study

“Eectiveness of care in German cancer centres” (WiZen) aims to close

this gap.

Methods: WiZen is a retrospective cohort study covering patients with

eight types of incident cancer in the period 2007-2017. e study is

based on nationwide health insurance data provided by WIdO (the AOK

research institute) and data from clinical cancer registries. Here, we report

results for patients with colon cancer (CC)/rectal cancer (RC) (ICD-

10-GM: C18-C20), and pancreatic cancer (PC) (ICD-10-GM: C25) based

on health insurance data. We estimated dierences in survival between

patients treated in GCS-certied cancer centers and non-certied hospi-

tals using relative survival analysis and applied Cox regression with shared

frailty to adjust for multiple patient (demographics, comorbidities and

indicators of tumor stage) and hospital characteristics.

Result: 109,518 patients with CC, 51,417 patients with RC, and 45,318

patients with PC were included. In line with relative survival analysis,

hazard ratios (HRs) derived from Cox regressions adjusting for potential

confounders on both the patient and the hospital level indicated a signi-

cantly lower hazard of death in patients treated in GCS-certied cancer

centers across all three cancer types (CC: HR=0.92, 95%-CI=0.89-0.95;

RC: HR=0.92, 95%-CI=0.88-0.95; PC: HR=0.89; 95%-CI=0.85-0.93).

Discussion: Drawing on a large sample and adjusting for multiple poten-

tial confounders, our ndings provide evidence that treatment in GCS-

certied cancer centers is related to better survival in patients with CC,

RC, and PC.

Conclusion: is observational evidence strongly suggests that certi-

cation of hospitals is a powerful means to improve patient outcomes in

cancer care.

Disclosure Statement: e authors declare no conict of interest.

535

Patient-individual tumor-derived models from CRC patients

and their potential in therapy prediction for CRC metastases

Christina Mullins; Sandra Wagner; Randy Przybylla; Florian Bürtin;

Michael Linnebacher

Universitätsmedizin Rostock, Allgemein-, Viszeral-, Thorax-, Gefäß- und

Transplantationschirurgie, Rostock, Deutschland

Background: Metastatic colorectal cancer (CRC) is a threatening diag-

nosis as overall survival is still very low. erefore, patients and physi-

cians are in need of better therapeutical options and enhanced therapy

response predictions. Our aim was to investigate the predictive capacity

of primary CRC tumor material for treatment responses of corresponding

metastases.

Methods: First, the mutational landscape of primary tumors and corre-

sponding metastases of 10 CRC patients was compared. Next, we investi-

gated cell line pairs of primaries and metastases for four of those patients

with regard to cell line characteristics and drug sensitivity. Finally, in a

proof of concept approach, PDX models of on patient were treated in vivo.

Result: Driver mutations did not dier between primaries and metasta-

ses but the latter tended to further accumulate mutations, many of still

uncertain signicance. In vitro chemosensitivity testing did not reveal

notable dierences in response to 5-FU and oxaliplatin between tumor

and corresponding metastasis cell lines. However, response to irinotecan

diered: the majority of investigated metastases-derived cell lines was less

sensitive to irinotecan than their primary tumor-derived cell line counter-

part. erapy recommendations based on these ndings were compared

with clinical treatment response and were oen in line with the predicted

therapy outcome.

Discussion: Primary tumor cell models seem to be a good tool to test

drug responses and draw conclusions for (potential) future metastases.

Conclusion: With an increasing number of data from tumor-derived cell

lines, such predictions could improve clinical treatment decisions, both

recommending likely most eective therapeutic options while excluding

ineective treatments and thus saving patients from side eects and early

development of resistant tumor cell clones.

Disclosure Statement: e authors declare no conict of interest.

539

Rectal Cancer and Risk of Secondary Cancer:

A Population-Based Study

Anne Schlesinger-Raab; Kathrin Halfter; Gabriele Schubert-Fritschle;

Jutta Engel

Tumorregister München (TRM) am Institut für Medizinische

Informationsverarbeitung Biometrie und Epidemiologie (IBE),

Ludwig-Maximilians-Universität München (LMU), München, Deutschland

Background: To investigate the risk of secondary cancer and therapy-in-

duced secondary primary cancer (SC) following primary rectal cancer

therapy.

Methods: All analyses were calculated on the basis of a population-based

cohort of rectal cancer patients diagnosed between 1998 and 2019 within

the catchment area of the Munich Cancer Registry (MCR). Cumulative

incidence (CI) with competing risks, survival analyses (overall (OS) and

relative (RS) survival), and multiple regression analyses (Fine-Gray)

were used to compare time periods (1998-2005, 2006-2013, 2014-2019),

sex and treatment. Analyses were similarly done on a propensity score

matched cohort.

Result: A total of 13,919 invasive primary M0 rectal cancer cases with

tumour resection were included. Median age of patients with or without

radiotherapy (RTX) diered between 65.0 yrs. and 70.3 yrs. In UICC

stage I, II and III, RTX was conducted in 10.7%, 48.9% and 59.3%, respec-

tively. 11,687 single rst M0 tumours were analysed for OS, RS and CI

of SC. 5-year OS/ RS improved from 69%/ 80% in the rst time period

to 74%/85% in the last. e 5-yr. CI of any SC was 6.1% in the rst time

period and decreased subsequently: in 2006-2013 the 5-yr. CI was 4.9%,

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 67

in 2014-2019 it was 4.0% (p<.0001). Sex dierences in 5-, 10- and 20-yr.

CI were distinct: 5.5%, 10.9% 18.5% in male, 4.6%, 8.8%, 14.9% in female

(p<.0001). Fine-Gray regression modelling of CI of SC found a small sig-

nicant eect of chemotherapy (CTX) increasing the risk of SC in total,

HR 1.22 (1.03-1.45) but no signicant eect of RTX. In men, a signicant

eect of RTX was found decreasing the risk of SC in the prostate, HR 0.46

(0.29-0.73). is eect for men was as well found in the PSM cohort.

Discussion: Although regression models were adjusted for age and

tumour characteristics, RTX in rectal cancer decreases the risk of prostate

cancer as a SC. e eect is also found in the analysed PSM cohort. A

plausible explanation is missing.

Conclusion: ere was no strong evidence for therapy-induced SC in rec-

tal cancer patients.

Disclosure Statement: e authors declare no conict of interest.

627

Plant polyphenols unexpectedly aggravate colon cancer liver

metastases via enhanced inammation

Johanna Roth1; Laura Robrahn1; Merve Erdem1; Athanassios Fragoulis2;

Ulf Peter Neumann1; Thorsten Cramer1

1Klinik für Allgemein-, Viszeral und Transplantationsmedizin, Uniklinik RWTH

Aachen, Aachen, Deutschland

2Institut für Anatomie, Uniklinik RWTH Aachen, Aachen, Deutschland

Purpose: Epidemiological data show reduced cancer incidence and

mortality in vegetarians. e benecial eect is thought to be mediated

partly by plant phytochemicals (PP). While a wealth of data show tumor-

inhibiting eects of PP in vitro and in immunodecient rodent models,

the consequences of these substances on tumor growth in mice with a

functioning immune system remain largely elusive.

Methods: Immunocompetent C57Bl6/J mice harboring liver metastases

(murine colon cancer cell line MC38) were gavaged once daily for 10 days

with a vegetable extract (VE) from garlic, beetroot, broccoli, Brussels

sprouts, cauliower, spinach and curcuma supplied with Epigallocatechin-

gallate from green tea. Tumors were counted and analyzed via immuno-

histochemistry (IHC).

Results: In vitro treatment of MC38 cells with the VE resulted in a

dose-dependent inhibition of proliferation and, ultimately, cell death.

Against this background we were intrigued to note that metastatic nod-

ules in the VE-treated mice were signicantly larger compared to water-

treated controls. IHC demonstrated signicant greater abundance of

leukocytes (CD45) and F4/80+ macrophages around the metastases in

the VE group. To address the functional importance of this nding, we

combined the VE with a an anti-inammatory agent (prednisolone). is

resulted in signicantly smaller metastases, supporting the idea that the

VE aggravates tumor formation via inammation.

Discussion: Our results conrm published data as they show anti- tumor

eects of PP in vitro. e unexpected nding of aggravated metastatic

growth in vivo upon oral supplementation with PP might be partly

explained by higher abundance of tumor-supporting leukocytes.

Conclusion: Our results once again demonstrate that results from cell cul-

ture studies and immunodecient rodent models have to be validated in

properly functioning animal models. e eects of PP on the immune sys-

tem are to be taken seriously and warrant further and thorough analysis.

Disclosure Statement: e authors declare no conict of interest.

718

Recapitulating Drug Treatment in a Dish - Investigating the

Impact of 2D Versus 3D In Vitro Cancer Models and Dierent

Treatment Schemes on Drug Response

Sushmitha Sankarasubramanian1,2; Anne-Claire Kröger3; Ulrike Pfohl1;

Jürgen Loskutov1; Michael Linnebacher4; Christian Regenbrecht1,5,6;

Lena Wedeken1

1CELLphenomics GmbH, Berlin, Deutschland

2Chirurgische Klinik, Universitätsklinikum Erlangen, Department of Surgery,

Erlangen, Deutschland

3Ruprecht-Karls-Universität Heidelberg , Fakultät für Biowissenschaften,

Heidelberg, Deutschland

4Universitätsmedizin Rostock, Chirurgische Klinik und Poliklinik, Molekulare

Onkologie und Immuntherapie, Rostock, Deutschland

5ASC Oncology GmbH, Berlin, Deutschland

6Universitätsklinikum Göttingen, Institut für Pathologie, Göttingen, Deutschland

Background: Cancer is a heterogenous disease and understanding the

disease biology and developing eective therapeutics benets greatly from

the use of suitable in vitro cell culture models. Established 2D lines have

been used as a base for discovery and proof of concept studies for the past

50 years (1, 2). In recent years, patient-derived 3D tumor models emerged

as a powerful tool to address cancer biology and assess drug sensitivity

(3, 4).

Methods: 2D colon cancer cell lines and thereof derived 3D colon cancer

models were treated with standard-of-care chemotherapeutics as well as

targeted therapies following the same protocol. In addition, for therapeu-

tic compounds given daily in clinic the eect of single vs daily dosing on

cancer cell drug sensitivity was evaluated. Cell viability measurement was

used to assess drug response.

Result: Drug response diered between cancer cell models cultured in 2D

and 3D, as well as between single and daily treatment schedules.

Discussion: Even though the use of 2D cell lines for testing of chemother-

apeutics and basic research is indisputable, patient-derived in vitro 3D

cancer models better recapitulate the cancer histology, genetic set up and

heterogeneity. In addition, drug sensitivity is inuenced by 2D versus 3D

culture conditions further questioning the use of 2D cell lines to mimic

tumor phenotype and functional activity.

Conclusion: e type of in vitro cancer model and drug treatment sched-

ule impact drug response. erefore, the selection of an appropriate

model and treatment scheme are crucial to derive data that can be used

for clinical decision making.

Indication of source

1. B. P. Lucey, W. A. Nelson-Rees, G. M. Hutchins, Arch Pathol Lab Med. 133,

1463–1467 (2009).

2. J.-P. Gillet, S. Varma, M. M. Gottesman, Jnci J National Cancer Inst. 105,

452–458 (2013).

3. M. Schütte et al., Nat Commun. 8, 14262 (2017).

4. G. Vlachogiannis et al., Science. 359, 920–926 (2018).

Disclosure Statement: e authors declare the following: Christian Regenbrecht

is shareholder at CELLphenomics GmbH, a company oering drug screens on or-

ganoid models, and ASC Oncology GmbH, a company involved in patient specic

therapy prediction.

726

Remarkable tumor response after addition of epidermal

growth factor receptor monoclonal antibody therapy

combined with irinotecan based chemotherapy in patient

with primary chemotherapy resistant metastatic colorectal

cancer with KRAS G13D mutation – A case report

Judith Gold; Jorge Riera Knorrenschild; Andreas Neubauer

Marburg, UKGM Marburg , Hämatologie/Onkologie, Marburg, Deutschland

Background: Additional treatment with EGFR antibody therapy can lead

to partial tumor regression in initially chemotherapy-resistant mCRC

with KRAS G13D mutation.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts68

Methods: A 30-year-old female presented with ileus. Emergency right

hemicolectomy followed showing an adenocarcinoma of coecum. MSS.

No BRAF- or NRAS-, but KRAS G13D mutation. Staging showed multi-

ple liver but no further metastases (UICC IVa).

Result: e liver metastases were considered non-resectable in local

tumorboard. We applied an aggressive chemotherapy regime (5 courses

FOLFOXIRI + Bevacizumab). 2 month later liver metastases were pro-

gressive. In primary chemotherapy-resistant tumor it is not expected that

2nd line therapy can lead to sucient response. Cetuximab is an EGFR

antibody which is ocially not approved for treatment KRAS mutated

mCRC because most studies predicted potential disadvantage to survival.

Discussion: Some studies suggested that KRAS G13D mutated tumors

may benet from cetuximab application combined with chemother-

apy better than tumors with other KRAS mutations 1²³. Regarding this,

Cetuximab was added while proceeding with FOLFOXIRI. Aer 6 courses

of FOLFOXIRI with Cetuximab instead of Bevacizumab staging showed

regressive metastases. PET-CT still showed active metabolism. Metastatis

were now considered resectable. Chemotherapy was continued due to ser-

vere side eects without Oxaliplatin and Irinotecan. Aer altogether 11

courses staging showed progressive disease, just before surgery could be

conducted. Aer no response to Lonsurf + Bevacizumab the patient died

12 month aer diagnosis.

Conclusion: It seems remarkable that in primary chemotherapy-resistant

mCRC with KRAS G13D mutation simply by switching antibody therapy,

tumor response could be achieved. Switching antibody therapy may be

considered for 2nd line treatment.

Indication of source:

1 Chen J et al. DOI: 10.1007/s00280-012-2005-9; 2 Mao et al. DOI: 10.1002/

cncr.27804; 3 McFall et al. DOI: 10.1126/scisignal.aaw8288

Disclosure Statement: e authors declare no conict of interest.

736

T stage-dependent lymph nodes (LN) and distant metastases

as well as accuracy of LN assessment in rectal cancer

Henry Ptok1; Frank Meyer2; Roland S. Croner2; Ingo Gastinger3;

Benjamin Garlipp3

1Dept. of General and Abdominal Surgery, Municipal Hospital (“Ernst-von-

Bergman-Klinikum”), Potsdam, Deutschland

2Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg,

Deutschland

3Intitute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Background: Up to now, investigation of a high number of lymph nodes

in rectal cancer was considered the basis of an accurate staging. However,

recently published data indicate that despite improved diagnostic of

lymph nodes no tumor stage migration can be found. In this context, the

authors have substantial doubt with regard to the “upstaging hypothesis”.

Aim: To analyze data obtained in a representative number of patients with

primary rectal cancer with regard to lymph node diagnostic and related

tumor stages.

Methods: In pT2-, pT3- and pT4 rectal cancer lesions, the impact of

investigated lymph nodes onto the frequency of pN+ status, the cumula-

tive risk of metachronous distant metastases as well as overall survival was

studied by means of a prospective multicenter observational study over a

dened period of time.

Results: From 2000-2011, the portion of surgical specimens with ≥ 12

investigated lymph nodes increased signicantly from 73.6 % to 93.2 %

(p<0.001) and the number of investigated lymph nodes from 16.2 onto

20.8 (p<0.001). Despite this, the percentage of pN+ rectal cancer lesions

varied only non-signicantly (39.9 % to 45.9 %; p=0.130; median, 44.1 %).

For pT2, pT3 and pT4 rectal cancer lesions, there was an increasing por-

tion of pN+ ndings correlating signicantly with the number of inves-

tigated lymph nodes up to n=12 investigated lymph nodes. Only in pT3

rectal cancer, there was a signicant increase of pN+ ndings in case of

> 12 lymph nodes (p=0.001) but not in pT2 (p=0.655) and pT4 cancer

lesions (p=0.256). For pT3 pN0 cM0 rectal cancer, risk of metachronous

distant metastases and overall survival did not depend on the number of

investigated lymph nodes.

Conclusion: In rectal cancer, at least n=12 lymph nodes are to be min-

imally investigated. e investigation of less lymph nodes is associated

with a higher risk of false-negative pN0 ndings. In particular, in pT3 rec-

tal cancer the investigation of more than 12 lymph nodes lowers the risk of

false-negative pN0 ndings. An up-staging eect by the investigation of a

possibly maximal number of lymph nodes could not be detected.

Disclosure Statement: e authors declare no conict of interest.

738

Can neoadjuvant chemoradiation (nCRT) be omitted in

patients with MRI-assessed, negative circumferential

resection margin in cT3 rectal cancer with multimodal

treatment - results of a prospective multi-center

observational study

Henry Ptok1; Frank Meyer2; Ingo Gastinger3; Benjamin Garlipp3

1Dept. of General and Abdominal Surgery, Municipal Hospital (“Ernst-von-

Bergman-Klinikum”), Potsdam, Deutschland

2Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg,

Deutschland

3Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Aim: To determine whether nCRT can be omitted in patients with MRI-

assessed cT3-rectal cancer and a negative mrCRM undergoing good-

quality TME.

Method: By means of a nationwide registry (n=43.147; prospective

multi-center observational study), patients with cT3-rectal cancer <12cm

from the anal verge with a negative (>1mm) MRI-assessed circumfer-

ential margin(CRM) undergoing radical resection from 2006-2008 were

selected. Overall, 87 patients were available for nal analysis (TME-alone,

n=25; nCRT+TME, n=62). Groups were balanced for age, sex, and ASA

score, with a non-signicant predominance of males in the nCRT+TME

group. Local and distant recurrence rates were compared between patients

undergoing primary surgery (TME-alone) vs. neoadjuvant chemoradia-

tion+surgery (nCRT+TME).

Results: In the TME-alone group, tumors were located closer to the anal

verge (p=0.018) and demonstrated a smaller minimal circumferential dis-

tance from the resection margin (p=0.036).

TME quality was comparable, as was median follow-up (48.9 vs. 44.9

months, p=0.268). Local recurrences occurred at a similar rate in the

TME-alone (n=1, 5.3%) and nCRT+TME groups (n=3, 5.5%) (p=0.994)

and were diagnosed at 10 months (TME-alone) and at 8, 13, and 18

months (nCRT+TME). Distant recurrences occurred in 28.9% and 17.4%,

respectively (p=0.626).

Analysis was limited to cT3-cancers with a negative mrCRM. In addition,

caution is required when appraising these results because of the limited

number of subjects, which adds uncertainty to the statistics.

Conclusions: In this cohort of patients with rectal cancer located <12 cm

from the anal verge and a negative mrCRM undergoing adequate TME,

omission of nCRT had no impact onto the local recurrence rate.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 69

742

Value of research on clinical care in oncological surgery using

the example of rectal cancer

Frank Meyer1; Roland S. Croner2; Hans Lippert2

1Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg;

Deutschland

2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg; Deutschland

In the process of the implementation of novel diagnostic and therapeutic

modes and procedures, data obtained in area-wide multi-center obser-

vational studies along the establishing period of time are indispensable.

is can be impressively detected considering the development of rectal

cancer surgery in Germany over a 10-years study period based on original

data from the Institute of Quality Assurance in Operative Medicine, Otto-

von-Guericke University at Magdeburg.

From 01/01/2000 to 12/31/2010, overall 33,724 patients with rectal cancer

were registered in Germany and evaluated according to quality assurance

aspects.

e main focus was directed onto the current trends, such as

colonoscopy-screening, MRI (assessing involvement of the circumferen-

tial resection margin [CRM]), endoscopic ultrasonography, neoadjuvant

treatment conzepts, total mesorectal excision [TME] and laparoscopy–

assisted surgical interventions as well as the early postoperative (rather

surgical/ operative) results and oncological long-term outcome.

References:

1. Gastinger I, Lippert H, Köckerling F, Dralle H (ed.). Chirurgische Qualitäts-

sicherung - Ergebnisse der klinischen Versorgungsforschung. eBook (2021)

http://www.aninstitut.de/de/Home.html [Zugri: 31. 08.2021]

2. Ptok H, Mundt A, Lippert H, Gastinger I. Rektumkarzinomchirurgie in

Deutschland – eine 10-Jahres-Übersicht auf der Grundlage der Daten des

AN-Instituts für Qualitätssicherung in der operativen Medizin gGmbH an

der Otto-von-Guericke-Universität Magdeburg. Zentralbl Chir 2013; 138 (4):

418–426

Disclosure Statement: e authors declare no conict of interest.

759

Multivisceral resection of advanced colon and rectal cancer:

A prospective multicenter observational study with

propensity score analysis of the morbidity, mortality and

survival #) - #) Initial data was published in “Chirurgische

Allgemeine” (issue 7+8/2021 published by “Kaden-Verlag”)

Hans Lippert1; Roland S. Croner1; Frank Meyer2; Ronny Otto1;

Karsten Ridwelski1

1Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

2Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg,

Deutschland

Aim: To analyze non-multivisceral resection (nMVR) vs. MVR ([partial]

resection of the tumor[Tu]-bearing organ along with resection of the

adherent adjacent organs or tissues) in terms of early postop. & long-term

oncological outcomes.

Method: Data of 25,321 patients (364 hospitals) who had undergone sur-

gery for CRC (UICC stages I–III) during a dened period were evaluated

in this prospective multicenter observational study.

Results: From 2008-2015, MVR rates were 9.9% (n=1,551) for colon

cancer (CA) & 10.6% (n=1.027) for rectal CA.

e MVR group had a high prevalence of intraop. (.,8%; 12.1%) & postop.

surgical complications (30.8 vs. 36.4%; each p<0.001).

Wound infections (colon CA: 7.1%) & anastomotic insuciencies (rectal

CA: 8.3%) frequently occurred aer MVR.

Morbidity rates of the MVR groups were also determined (43.7 vs. 47.2%).

Hospital lethality was 4.9% in the colon CA-related MVR group & 3.8%

in the rectal CA-related MVR group & was signicantly increased com-

pared with those of the nMVR group (both p<0.001). Results of the MPA

showed that the morbidity in both MVR groups (colon CA: 42.9 vs. 34.3%;

rectal CA: 46.3 vs. 37.2%; each p<0,001) was signicantly increased.

Hospital lethality tended to increase in the colon CA-related MVR group

(4.8 vs. 3.7%; p=0.084), while it signicantly increased in the rectal

CA-related MVR group (3.4 vs. 3.0%; p=0.005).

Moreover, 5-yr overall survival rates were 53.9% (nMVR: 69.5%; p<0.001)

in the colon CA group & 56.8% (nMVR: 69.4%; p<0.001) in the rectal CA

group.

Risk factors common to both Tu types were advanced age (>79 yr), pT

stage, sex & morbidity (each hazard ratio: >1; p<0.05).

Conclusion: MVR allows curation by R0 resection with adequate long-

term survival. For colon or rectal CA, MVR tended to be associated

with reduced 5-yr overall survival rates (signicant only for pT4 colon

CA based on the MPA results, not shown), as well as, with a signicant

increase of morbidity in both Tu entities. In the overall data, MVR was

associated with signicant increases in hospital lethality, as indicated by

the MPA (signicant only for rectal CA).

Disclosure Statement: e authors declare no conict of interest.

761

Distinct mircobiomes in right- and left-sided colon cancer

Melanie C. Langheinrich1, Stefan Wirtz2, Barbara Kneis3, Klaus Weber4,

Maximilian Brunner4, Christian Krautz4, Jonel Trebicka5, Abbas Agaimy6,

Robert Grützmann4, Stephan Kersting1

1Universitätsmedizin Greifswald, Klinik für Allgemeine Chirurgie, Viszeral-

Thorax- und Gefäßchirurgie, Greifswald, Deutschland

2Universitätsklinikum ERLANGEN, FORSCHUNGSABTEILUNG Medizinische

Klinik1, Erlangen

3Universitätsklinikum Erlangen, Medizinische Klinik, Erlangen, Deutschland

4Universitätsklinikum Erlangen, Klinik für Allgemein- und Viszeralchirurgie,

Erlangen

5Universitätsklinikum Frankfurt, Sektion Translationale Hepatologie,

Medizinische Klinik 1, Frankfurt

6Universitätsklinikum Erlangen, Institut für Pathologie, Erlangen

Background: Colorectal cancer (CRC) is the third leading cause of cancer

death worldwide. Biologically CRC is a heterogeneous group. e patho-

genesis is complex and includes various genetic and epigenetic alterations.

It is widely accepted that tumor location (right- le-sided colon cancer,

RSCC, LSCC) is a crucial factor in determining disease progression and

inuences disease management. e rate of CRC rises among people aged

under 50. Changes in the incidence of a disease by generation, suggests

that the cause is environmental rather than biological. A number of envi-

ronmental factors play a role in carcinogenesis, including the microbiome.

Methods: e study population consists of 41 patients (RSCC 24, LSCC

17) from the prospective Erlanger microbiome study. Microbiota proles

(tumor; proximal resection margin (ileum, healthy colon), distal resec-

tion margin (healthy colon, rectum) and stool) were characterized by

amplication of the V3/V4 region of the 16SrRNA gene followed by deep

sequencing and biostatistical analysis.

Result: e overall structure of the microbiome was signicantly dierent

(alpha diversity Observed index: p value< 0.001) and beta diversity (PCoA:

p value< 0.001). e stool microbiome only partly reects the microbiome

of CC. e tumor microbiome of RSCC and LSCC showed a signicantly

dierent diversity (Chao1 index: p value: 0.01). Linear discriminant anal-

ysis (LDA) coupled with eect size measurements (LEfSe) was applied

to determine key taxa and 10 genera were identied. Furthermore, we

revealed a tumor-microbiome-ileal microbiome association.

Discussion: e microbiome puzzle is far from being solved. Most

microbiome studies used fecal rather than tumor or mucosal samples

and considered CRC as one disease group. Compositional alterations in

the microbiome are not restricted to dierent microhabitats, they dier

between RSCC and LSCC.

Conclusion: Collectively, our results provide new insights into the com-

plex microbiome landscape of CC.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts70

793

Does intestinal anastomosis in resection of colon cancer have

a signicant impact onto long-term survival?

Frank Meyer1, Ellen Hajduk2, Karsten Ridwelski2

1Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg,

Deutschland

2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg with University Hospital, Magdeburg, Deutschland

Ziel: Analyse d. Einusses der Op-Technik (-/+ Darmanastomose)

& -Dringlichkeit von planbarer vs. Notfall-Op auf das frühpostop.

(Morbidität/Letalität) & Langzeit-onkochir. Outcome (5-J-Gesamt-/-Tu-

freies Überleben sowie -Lokalrezidivrate)

Methode: Prospektive multizentr. Observat.-Studie z. Erfassung aller

konsekutiven Patienten(Pat.) mit primärem Colon-CA

Ergebnisse: Von 2010–2016 wurden 14.466 Pat. erfasst (717 [4,96%] in

“matched-pair”-Analyse einbezogen). 12.620 Pat. (87,2%) wurden elek-

tiv operiert unabhängig davon, ob eine Darmanastomose od. ein Anus

praeter(AP) angelegt wurde; Notfall - mehrheitlich (n=1.332 Pat.; 72,1%)

Darmanastomose möglich vs. 514 Individuen (27,9%) mit Notfall-OP,

die einen AP erhielten (noch seltener b. geplant op. Pat. AP erforderlich:

n=366 [3%]).

Pat., die eine AP-Anlage erhielten (wesentl. Einuss des präop. AZ)

erhielten od. im Notfall operiert wurden, wiesen ein nachteilig-

eres Risikoprol (art. Hypertonie, Diab. mell., kardiale od. renale

Nebenerkrankg.) auf - was nicht zuletzt die Diskontinuitätsresektion mit

rechtfertigte - und entwickelten häuger Komplikationen.

Neben der postop. Letalität (insbes. auch auf die allg. Komplikationsrate

zurückzuführen) wurden als wichtigste Ein.-Faktoren auf das

Langzeitüberleben Alter & Tu-Stadium sowie der R-Status ermittelt - je

fortgeschrittener der Tu, desto geringer el das Langzeitüberleben aus.

Die Kaplan-Meier-Kurven für die Op-Technik & Dringlichkeit zeigten

in der matched-pair-Analyse, dass Pat. mit gl. Tu-Stadium/Alter/

Risikofaktoren eine signif. bessere Überlebenschance haben, wenn sie

elektiv bzw. mit Darmanastomose operiert werden.

Multivariable Analyse: Ältere Pat. mit (lediglich) einer AP-Anlage zeigten

ein besseres Outcome.

Schlussfolgerung: Es werden Lit.-Angaben zum signif. Zusammenhang zw.

op. Komplikationen & Letalität sowie Vorerkrankg. & Komplikationsrate

bestätigt sowie, dass ältere Pat. in einem red. AZ (entspr. ASA-Scoring)

eher von einer Diskontinuitätsresektion (AP-Anlage) protieren wie auch

b. Fern-Mts.

Disclosure Statement: e authors declare no conict of interest.

799

The impact of the COVID-19 pandemic on the diagnosis and

medical care of colorectal cancer patients in Saxony - analyses

for the CancerCOVID consortium

Thomas Birkner1, Falko Tesch1, Martin Seifert1, Olaf Schoer1,

Jan Schildmann2, Anke Reinacher-Schick4, Jochen Schmitt3

1Zentrum für Evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und

Medizinische Fakultät Carl Gustav Carus an der Technischen Universität Dresden,

Dresden

2Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-

Luther Universität Halle-Wittenberg, Uniklinikum Halle, Halle

3Zentrum für Evidenzbasierte Gesundheitsversorgung, Medizinische

Fakultät Carl Gustav Carus der Technischen Universität Dresden, Professur für

Sozialmedizin und Versorgungsforschung, Dresden

4Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität

Bochum, Medizinische Klinik V für Hämatologie und Onkologie mit

Palliativmedizin, Bochum, Deutschland

Background: e focus on treatment of COVID-19 patients during

the Sars-CoV-2 outbreak, lockdown measures and individuals’ anxiety

regarding potential infection when seeing a healthcare provider have

likely implications on the extent of diagnosis and quality of treatment of

non-COVID-19 patients. is hypothesis has been evaluated exemplarily

for the early detection, diagnosis and treatment of colorectal cancer in

Saxony within the framework of the CancerCOVID project.

Methods: e situation during 2020 was compared with the situation

before the Sars-CoV-2 pandemic (i.e., 2019). e evaluation is based

on pseudonymised routine statutory health insurance data for Saxony

including more than 50% of the population.

Result: A main nding was the drop in the number of diagnosis of new

colorectal cancer cases between 2019 and 2020 (i.e., 1797 versus 1352).

Furthermore, the per-patient rate of surgeries for incident colorectal

cancer cases increased slightly (2.4 to 2.5), as did the rate of intravenous

(IV) cytostatics administration (2.2 to 2.4) and radiation therapy (1.1

to 1.4). e per-patient rate of surgeries for prevalent colorectal cancer

patients remained constant (0.3), as did the rate of radiation therapy (0.2).

However, the per-patient rate of IV cytostatics for prevalent colorectal

cancer patients decreased from 1.7 to 1.4. e results of analyses pertain-

ing to cancer screenings and mortality are available as well.

Discussion: It is likely that reduced screenings and fewer contacts with

healthcare providers due to the pandemic led to the drop in new diagno-

sis. e reasons for the small numeric increases in the rates of procedures

per incident patient versus the largely at trajectory in the rate of health

care services for prevalent cases require further exploration.

Conclusion: COVID-19 was associated with changes in the provision of

health care especially for cancer patients, which should be taken into con-

sideration in the resource planning when preparing for another pandemic

or public health emergency.

Disclosure Statement: e authors declare the following: consultant

808

In vitro and in vivo characterization of the novel PFKFB3

inhibitor KAN0438757 in colorectal cancer

Tina Goldhardt1; Marcus Edelmann1; Tiago de Oliveira1; Annalen

Bleckmann2; Kerstin Menck2; Lutz Ackermann3; Torben Rogge3; Tim

Beissbarth4; Michael Ghadimi1; Lena-Christin Conradi1

1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral-, und

Kinderchirurgie, Göttingen, Deutschland

2Universitätsklinikum Münster - UKM, Medizinische Klinik A, Münster,

Deutschland

3Georg-August-Universität Göttingen - Fakultät für Chemie, Institut für

organische und biomolekulare Chemie, Göttingen, Deutschland

4Universitätsmedizin Göttingen, Institut medizinische Bioinformatik, Göttingen,

Deutschland

Background: Rectal cancer is routinely treated by neoadjuvant radio-

chemotherapy followed by surgical resection. Less than 20% of patients

show a complete pathological response upon this regimen. It was previ-

ously shown that glycolytic inhibition via targeting of PFKFB3 results in

tumor vessel normalization. A novel PFKFB3 inhibitor (KAN0438757)

was shown to have radio- and chemosensitizing capacity. We here eval-

uate KAN0438757 in vitro and in vivo in combination with standard

chemotherapy.

Methods: Human CRC cell lines (HCT-116, HT-29) and endothelial cells

(HUVECS) were subjected to KAN0438757 alone or in combination with

chemotherapy. Proliferation, cell death, migration and invasion were

assessed. KAN0438757 was also tested in healthy C57BL/6 mice for its tox-

icity prole before performing treatments in PDX using NOD-SCIDprkdc

mice to explore eects on tumor growth and tumor vascularization.

Result: We found a concentration dependent antiproliferative eect of

KAN0438757. Migration as well as the invasive capacity were signi-

cantly reduced, independently of the antiproliferative eect. KAN0438757

alone showed no high-grade toxicity in healthy mice. When combining

KAN0438757 with chemotherapy we observed a synergistic anti-tumor

eect and signs of tumor vessel normalization.

Discussion: As PFKFB3 is overexpressed in CRC but also in endothe-

lial cells, we speculated that KAN0438757 mainly targets the tumor while

leaving non-transformed cells unaected. Since high-dose inhibition of

PFKFB3 can aect tumor cells, low-dose treatment leads to tumor vessel

normalization. When using a low concentration of KAN0438757, eects

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 71

on tumor growth were visible in combination with chemotherapy, but not

upon KAN0438757 alone.

Conclusion: KAN0438757 showed a clear antiproliferative eect in rectal

cancer cells and PDX without being overly toxic in vivo. It showed promis-

ing synergistic ecacy when used in combination with chemotherapy and

therefore should be further tested in vivo.

Disclosure Statement: e authors declare no conict of interest.

815

Molecular consensus subtyping of colorectal carcinoma In

liver and brain metastases

Carolin Krekeler1; Barnabas Irmer1; Suganja Sivaloganathan1;

Kerstin Menck1; Micha Peeck1; Darius Wlochowitz2; Lena-Christin

Conradi3; Astrid Wachter2; Michaela Bayerlova2; Alexander Wol2;

Hans-Ulrich Schildhaus4; Christine Stadelmann-Nessler5;

Martin Proescholdt6; Kia Homayounfar3; Tobias Pukrop6,7; Tim Beissbarth2;

Annalen Bleckmann1,7

1University Hospital Münster, Dept. of Medicine A, Hematology, Oncology and

Pneumology

2University Medical Center Göttingen, Dept. of General, Visceral and Pediatric

Surgery

3University Medical Center Göttingen, Dept. of Medical Statistics

4University Hospital Essen, Institute for Pathology

5University Medical Center Göttingen, Dept. of Neuropathology

6University Medical Center Regensburg, Dept. of Internal Medicine III,

Hematology and Medical Oncology

7University Medical Center Göttingen, Dept. of Hematology and Medical

Oncology

Background: Inter-metastatic heterogeneity in patients suering from

colorectal carcinoma (CRC) is discussed as a cause for diverse clinical

outcomes. erefore, this study aimed to identify prognostically relevant

characteristics of CRC-derived metastatic tissue samples from brain and

liver at the transcriptome and proteome level. ereby we additionally

strived to better understand processes of metastatic organotropism to

ultimately nd new potential cancer vulnerabilities for targeted therapy

in CRC patients.

Methods: Tissue samples from 61 CRC patients with liver or brain metas-

tases were collected and analyzed by RNA sequencing (RNA-Seq) as well

as reverse phase protein array (RPPA). e expression levels of selected

dierentially expressed genes were further quantied by RT-qPCR and

immunohistochemistry. All metastases were annotated according to the

previously described consensus molecular subtype (CMS) classication.

e resulting CMS proles were correlated with the overall survival of

CRC patients.

Result: CRC metastases in liver and brain were signicantly dierent (p

<0.001) when comparing the corresponding RNA and protein signatures.

Liver metastases showed enriched amounts of the mesenchymal CMS4

subtype, which was shown to be prognostically favorable (p = 0.018) with

a 3-year survival of 73.3% of patients aer metastases resection. In con-

trast, most brain metastases were assigned to the metabolic CMS3 sub-

type, which was further conrmed by quantifying the expression levels

of selected metabolic genes on RNA and protein level within the corre-

sponding tissue samples.

Conclusion: Transcriptomic evaluation and CMS-based classication of

dierent CRC metastases revealed an inter-metastatic heterogeneity with

organ-specic CMS-signatures and evident impact on patient’s survival.

We identied a metabolic signature of CRC-derived brain metastasis that

might be exploited by upcoming studies to nd new therapeutic targets

for those patients.

Disclosure Statement: e authors declare no conict of interest.

864

Pathological function of neutrophil extracellular traps in

human colon cancer

Antonia Margarethe Stehr1; Guangxia Wang1; Richard Demmler1;

Marc P Stemmler2; Philipp Tripal3; Carol I Geppert4; Susanne Merkel5;

Martin Herrmann6,7; Michael Stürzl1,8

1Friedrich-Alexander University (FAU) Erlangen-Nürnberg and

Universitätsklinikum Erlangen, Department of Surgery, Division of Molecular

and Experimental Surgery, Translational Research Center, Erlangen, Deutschland

2Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Nikolaus-Fiebiger

Center for Molecular Medicine, Department of Experimental Medicine I,

Erlangen, Deutschland

3Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Optical Imaging

Centre, Erlangen, Deutschland

4Friedrich-Alexander University (FAU) Erlangen-Nürnberg and

Universitätsklinikum Erlangen, Institute of Pathology, Erlangen, Deutschland

5Friedrich-Alexander University (FAU) Erlangen-Nürnberg and

Universitätsklinikum Erlangen, Department of Surgery, Erlangen, Deutschland

6Friedrich-Alexander University (FAU) Erlangen-Nürnberg and

Universitätsklinikum Erlangen, Department of Internal Medicine 3, Erlangen,

Deutschland

7Friedrich-Alexander University (FAU) Erlangen-Nürnberg and

Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie (DZI),

Erlangen, Deutschland

8Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN,

Erlangen, Deutschland

Background: Neutrophil extracellular traps (NETs) are extracellular

structures formed by neutrophils, consisting of their DNA and proteins.

Although originally described as a defense mechanism to kill bacteria,

NETs have been reported to negatively inuence various kinds of diseases,

including cancer. However, especially data on intra-tumor NET presence

is very limited and the association of tissue NETs with clinically relevant

parameters remains unclear. We therefore sought to establish and vali-

date a robust method of intra-tumor NET detection and investigate the

relation between tissue NET presence and clinical features of colorectal

carcinoma (CRC) patients.

Methods: NET presence in colon cancer tissues from 85 patients was

assessed by staining formalin-xed paran-embedded tissue sections

for neutrophil elastase, citrullinated histone H3 (H3cit), histone H2B

and extracellular DNA (using a large IgM anti-DNA antibody). Staining

was evaluated by laser-scanning microscopy and partly by high-resolu-

tion stimulated emission depletion (STED) microscopy. Further, CRC cell

lines were incubated with in vitro generated NETs from human isolated

neutrophils to investigate direct eects of NETs on cancer cells.

Result: H3cit was sucient to detect intra-tumor NET formation, which

was commonly present in colon cancer tissues (37/85, 44%). In most

cases, tumor inltrating NETs were located in both the tumor center and

the invasive front or in the tumor center only. Remarkably, the presence

of NETs signicantly correlated with high tumor grades and locoregional

metastases. In addition, NETs were found to induce migration, pseudo-

podia formation and epithelial-mesenchymal transition (EMT) in CRC

cells, in vitro.

Discussion: We oer an easy-to-use tool for the evaluation of intra-tumor

NET presence. Further, our results support the association of tumor inl-

trating NETs with unfavorable clinical characteristics, indicating that they

might contribute to tumor progression.

Conclusion: NETs present as a promising therapeutic target in CRC.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts72

866

Upfront surgery in upper rectal cancer– TME or

PME? - Impressions from a single GAST-05-study site

Laura Regina Werle1, Andreas Leha2, Friederike Braulke3,4,

Johanna Kreutzer1, Tatiana Grammatikopoulou1, Charlotte de Boer1,

Torsten Liersch1

1Department of General, Visceral and Pediatric Surgery, University Medical

Center of the Georg August University of Göttingen, Göttingen, Deutschland

2Institute for Biostatistics and Biometry, University Medical Center of the Georg

August University of Göttingen , Göttingen, Deutschland

3Department of Hematology and Medical Oncology, University Medical Center

of the Georg August University of Göttingen, Göttingen, Deutschland

4Comprehensive Cancer Center, University Medical Center of the Georg August

University of Göttingen, Göttingen, Deutschland

Background: To evaluate whether total (TME) or partial mesorectal

(PME) excision is required for stage II/III cancer in the upper rectum (≥

12 cm above anal verge) according to the GAST-05 randomized multi-

center phase II trial (ISRCTN35198481)

Methods: Surgery was performed in 98 (median age: 69 years) partici-

pants of the most recruiting GAST-05-study site randomized to TME

(control) vs. PME (experimental). Based on standardized staging, surgical

procedures were evaluated in terms of feasibility, peri-/postoperatively

determined quality, and of acute and/or long-term adverse events using

NCI-CTCAE-criteria (vs 3.0). Various clinicopathological parameters

(such as safety margin, circumferential resection margin (CRM), conver-

sion between TME and PME, technique of anastomosis) were included in

survival analyses using Logrank test, Kaplan-Meier estimator, and mul-

tivariable Cox proportional hazard regression models to test interaction

eects of selected predictors.

Result: TME (44.9%) and PME (55.1%) were performed in 82.7, 16.3 and

1%, respectively, with good, moderate, or poor quality. R0 and negative

CRM (≥ 2 mm) status were achieved in 95.5, 98.1, 72.7, and 66.7% aer

TME and PME, respectively. e 60-day mortaliy was 1.0%. During the

follow-up period of 60 months, 264 adverse events (AEs) were docu-

mented, 179 aer TME and 54 aer PME. e most frequently AEs (grade

1 to 4) were diarrhea (TME: 49.1%; PME: 42.9%), erectile dysfunction

(TME: 21.2%; PME: 25.8%) and fecal incontinence (TME: 20.1%; PME:

15.2%). Restrictive mean value of RFS for stage II patients (108.9 months)

was signicantly better than for stage III (78.7 months; p<0.001). Tumor

inltration depth (< 5 vs. ≥ 5 mm; p = 0.031) and age (p = 0.005) had an

impact on RFS (univariable models). Results from the multivariable sur-

vival analyses will be presented at the DKK.

Discussion: Surgical quality and safety margins in PME have an impact

on RFS, PME seems to be not inferior to TME in upper rectal cancer.

Conclusion: TME is associated with more postsurgical complications vs.

PME.

Disclosure Statement: e authors declare no conict of interest.

867

Treatment Patterns in Patients with BRAF V600E mutant

metastatic colorectal carcinoma: German and Austrian

Subgroups from the CAPSTAN CRC retrospective study

Isabel Virchow1; Susanna Hegewisch-Becker2; Arndt Nusch3;

Lutz Jacobasch4; Gerald Prager5; Jörg Tschmelitsch6; Manfred Welslau7;

Thomas Wol8; Frank Reichenbach9; Dirk Arnold10

1Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, Essen, Deutschland

2Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Hamburg, Deutschland

3MVZ für Hämatologie und Onkologie, Ratingen, Deutschland

4Gemeinschaftspraxis Hämatologie und Onkologie, Dresden, Deutschland

5Medical University of Vienna, Vienna, Österreich

6Hospital Barmherzige Brüder, St. Veit an der Glan, Österreich

7Oncological Practice Aschaenburg, Aschaenburg, Deutschland

8OncoResearch Lerchenfeld, Hamburg, Deutschland

9Pierre Fabre Pharma GmbH, Freiburg, Deutschland

10Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Deutschland

Background: BRAF V600E mutant metastatic colorectal cancer (mCRC)

is associated with a poor prognosis. Current European guideline recom-

mendations for this population are mostly based on small cohorts due to

limited clinical data.

Methods: CAPSTAN is a retrospective study evaluating rst-line treat-

ment patterns, eectiveness and safety of BRAF V600E-mutant mCRC

treatment in 7 European countries initiated between 2016 and 2018. Here,

systemic treatment patterns of the German (D) and Austrian (A) sub-

groups were analyzed.

Result: 49 pts (D/A: N [%]: 45[18]/4[2]) were enrolled in D and A with

amedian age of 66 (D) and 62 years (A). In D and A, ca. half of the tumors

were right-sided and MSI-high status was noted for 27% of pts in D. Main

regimens in 1st-line were folinic acid/uorouracil (FOLF) and oxaliplatin

(OX) (FOLFOX) + bev (D/A [%]: 36/25), FOLFOX alone (D 18%), FOLF

plus irinotecan (IRI) (FOLFIRI) + bev (D/A [%]: 13/50), or FOLFOXIRI +

bev (D/A [%]: 13/25). CT + anti EGFR (cetuximab or panitumumab) was

used in 9% of pts in D. Median duration of 1st-line treatment was 4.7 and

2.2 months (D/A). 49% of pts enrolled in CAPSTAN overall had at least

1 treatment-related, adverse event considered relevant in 1st-line (RAE),

including diarrhea (12%), peripheral neuropathy (8%), neutropenia (7%),

asthenia (6%), and nausea (6%). Most RAEs occurred under triplet CT +/-

targeted therapy (TT; anti VEGF or anti EGFR). 62 and 75% of pts con-

tinued to at least 2nd-line (D/A). Details on 2nd and further treatment lines

and comparison to the CAPSTAN total population will also be reported.

Discussion: Based on the CAPSTAN study, 1st line treatment of BRAF

V600E-mutant mCRC pts in D and A mainly consists of CTs + targeted

agents. Both anti-VEGF and anti-EGFR are used in this treatment setting.

Most RAEs were associated with TT + triplet CT backbone.

Conclusion: In line with updated DGHO guideline recommendations,

doublet CT was used as the preferred backbone for anti-VEGF treatment.

Indication of source

1 Virchow I. et al., DGHO congress 2022, abstract #28

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 73

Poster

Gastrointestinal (Colorectal) Cancer

897

Successful introduction of a point mutation into the genome

of a primary colon cancer cell line using CRISPR base editing

technology

Bakr Mustafa; Abdelouahid Maghnouj; Stephan Hahn

Ruhr universität Bochum, Department of Molecular Gastrointestinal Oncology,

Bochum, Deutschland

Novel CRISPR/Cas9 genome base editing technology is a powerful DNA

editing. Many eorts have been made to investigate the editing eciency

of CRISPR base editing system. However, the editing eciency of stably

expressed base editors in primary tumor cell lines is not well studied due

to lentivirus packaging limitations and the low transduction eciency of

primary tumor cell lines.

Here, we generated a lentiviral adenine base editor vector that has a ex-

ible NGN PAM recognition site. To study its editing eciency, we have

developed a GFPstop reporter gene which was subsequently introduced

into the genome of the primary cell line. we have used a 50x concentrated

lentivirus for the delivery of the adenine base editor. we compared the

editing eciencies of a non-inducible sgRNA expression vector and an

inducible sgRNA.

We found a highly stable expression of the adenine base editor in a pri-

mary colon cancer cell line. In addition, the adenine base editor success-

fully modied the endogenous GFPstop transgene to reverse the stop

codon into glutamine (TAG>CAG). FACS detected 15% GFP positive

cells using non-induced sgRNA three days aer transduction and up to

5% GFP positive cells were found using an inducible sgRNA aer three

days of induction with doxycycline. To investigate the ability of the ade-

nine base editor to target an endogenous gene, we targeted KRAS codon

61. Adenine base editor successfully introduced KRAS Q61R mutation

CAA>CGA. We were able to detect 1.5% allele frequency for the KRAS

Q61R mutated allele using ddPCR. Sanger sequencing conrmed the

introduction of KRAS Q61R point mutation.

Our study demonstrates the ecient introduction of a point mutation in

the genome of primary colon cancer cell line using a stable expression

of CRISPR/Cas9 base editing system. High virus concentration and the

use of a non-inducible sgRNA vector are potential important parameters

for ecient editing. is strategy should be useful to study the biology of

oncogenic mutations under the control of its endogenous promoter with-

out the need for classical transgenic animal technology.

Disclosure Statement: e authors declare no conict of interest.

947

Findings in a young group with familial colorectal risk: Results

of the FARKOR study

Alexander Crispin1; Sabine Homann1; Raael Rehms1; Doris Lindörfer1;

Lara Hallsson2; Nikolai Mühlberger2; Beate Jahn2; Uwe Siebert2;

Gaby Sroczynski2; Ulrich Mansmann1

1IBE, LMU München, München, Deutschland

2Institute of Public Health, Medical Decision Making und Health Technology

Assessment, UMIT – Private University for Health Sciences, Medical Informatics

and Technology, Hall i. Tirol, Österreich

Purpose: Colorectal cancer (CRC) screening in Germany starts at age 50.

As there is evidence that individuals with a family history of CRC have an

increased risk of developing CRC before age 50, screening for this group

should start earlier. FARKOR (FAmily Related COlorectal cancer Risk)

evaluates the clinical and economic eects of a risk-adapted screening

program for CRC in individuals between 25 and 50 years of age.

Methods: Our nal analysis assesses the eects of FARKOR in a popu-

lation-based prospective cohort study. e program was open to mem-

bers of the statutory health insurance in Bavaria (aged 25 to 49 years)

between October 2018 and March 2021. Participants entered the study

through their physicians or a public campaign. Additionally, sickness

funds contacted recently diagnosed CRC patients to inform them about

the potentially increased CRC risk of their relatives. Trained doctors clas-

sied participants as potential risk carriers or as inconspicuous. Potential

risk carriers were invited to make a shared decision with their doctors on

1) an immunological fecal occult blood test (iFOBT) or 2) a screening

colonoscopy.

Results: During the program, 25,848 eligible patients joined the pro-

gram. Among the 5,769 identied potential risk carriers, 1,188 received

an iFOBT, while 1,595 underwent a colonoscopy. 287 patients with ade-

nomas (76 of them advanced) were identied (18.0% of the participants).

Four patients had CRC (0.25%). Record linkage with insurance data

revealed these numbers to be underestimates, since screening procedures

initiated by FARKOR but performed outside the program were not docu-

mented in the study database. Colonoscopy complications were limited to

four bleedings that could be treated conservatively.

Conclusions: Our results show good adherence to the proposed screen-

ing measures. Detection rates resemble screening programs in older

populations.

Disclosure Statement: e “German Innovation Fund” of the Federal Joint Com-

mittee (G-BA) supports this work: 01NVF17026. e authors declare no conict

of interest.

955

Consistency of familial risk proles between questionnaire

and interview based risk assessment in a screening

population: Results from the FARKOR study

Ulrich Mansmann1; Sabine Homann1; Raael Rehms1; Doris Lindörfer1;

Lara Hallsson2; Beate Jahn2; Nikolai Mühlberger2; Gaby Sroczynski2;

Uwe Siebert2; Alexander Crispin1

1IBE, LMU München, München, Deutschland

2Institute of Public Health, Medical Decision Making und Health Technology

Assessment, UMIT – Private University for Health Sciences, Medical Informatics

and Technology, Department of Public Health, Health Services Research and

Health Technology Assessment, Hall i. Tirol, Österreich

Background: FARKOR1 is a population based observational study to

motivate young persons with familial CRC risk (fCRC) to prevent CRC.

e study uses a two-step selection process to asses fCRC by a ques-

tionnaire and an interview-based evaluation. It was of interest to study

the consistency of risk assessments between both steps and information

gained from family trees (FT).

Methods: FARKOR recruited young members of the statutory health

insurance in Bavaria between October 2018 and March 2021. Trained

doctors classied participants as potential risk carriers starting with a

questionnaire2 (Q), followed by an interview (I).

Result: A total of 25,848 subjects participated (70.0% female, mean age

37.2 y) of whom 5,769 (22.3%) had a Q based fCRC (70.0% female, mean

age 39.0 y). About 13.7% documented only 2nd grade relatives, 6.1% only

1st grade relatives, and 2.5% 1st and 2nd grade relatives with CRC diagnosis.

A total of 3,162 (58.0%, n=5,769) subjects underwent I based risk assess-

ment. e criteria based consistency between Q und I ranged between

74.4% and 78.7%. A total of 2504 FTs were documented. For 5 criteria,

consistency between Q and FT ranged between 63.0% and 87.1% and

between I and FT between 79.9% and 92.5% respectively.

Discussion: Agreement between Q and I based assessment is about 75%.

Compared to FT documented information during the interview, Q based

consistency is less than the I based risk assessment which was simultane-

ously assessed with the FTs. e prevalence of familial CRC risk as found

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts74

in the FARKOR population cannot be generalized because of unclear

selection mechanisms with which participants were recruited.

Conclusion: e observed inconsistencies demonstrate the need to train

persons to be screened as well as medical personnel in assessing objective

disease information from family histories.

Reference:

1. Homann S et al BMC Gastroenterol 2020,20(1):131. doi: 10.1186/s12876-020-

01247-6.

Disclosure Statement: e “German Innovation Fund” of the Federal Joint Com-

mittee (G-BA) supports this work: 01NVF17026. e authors declare no conict

of interest.

963

Intraoperative ICG uorescence identies colorectal liver

metastaseswith complete response after chemotherapy

Oliver Stöltzing

Elblandklinikum Riesa, Elblandkliniken, Allgemein- und Viszeralchirurgie,

Riesa,Deutschland

Background: Patients with multifocal colorectal liver metastases (CRLM)

oen receive systemic therapy prior to surgery. At the time of re-staging,

CRLM may become undetectable by imaging aer chemotherapy, i.e. dis-

appearing liver metastases (DLM). But DLM does not necessarily equal

pathological complete remission (CR). An increasing number of patients

with DLM is presented in tumor conferences, confronting surgeons with a

dicult dilemma: to resect or to not resect the original sites of DLM? e

aim of this investigation was to evaluate the role of ICG-uorescence in

liver surgery to identify colorectal DLM.

Methods: For ICG-analysis of CRLM and suspected CR, patients (n=3)

with initial multifocal disease received 5 mg of indocyanine green (ICG)

24-72h prior to laparoscopic surgery. Fluorescent – anatomy was visual-

ized by using the Storz ICG-system or Pinpoint/Stryker. Multiple acces-

sible lesions were excised per patient by minimal-invasive liver surgery.

Resected specimen were sectioned, photographed and histologically

examined.

Result: In all three patients with DLM, ICG-uorescence was able to iden-

tify the original metastatic sites. In one patient, excised lesions showed

persistent vital tumor cells. However, in 2 patients, histology revealed a

full pathological remission with no vital tumor areas within the excised

ICG-positive lesions.

Discussion: is is the rst report to demonstrate that colorectal liver

metastases preserve an ICG-positive rim aer pathological complete

remission. is nding can substantially contribute to dening the appro-

priate oncologic concept in patients with multifocal CRLM and DLM aer

chemotherapy. us, when identifying ICG-positive reference lesions with

pathological CR, a watch and wait strategy may rather be recommended

than major liver surgery of entire original sites of metastases.

Conclusion: ICG-uorescence is valuable for detecting occult CRLM aer

chemotherapy and may impact clinical decision making in liver surgery.

Disclosure Statement: e author declares no conict of interest.

1006

Role of oxaliplatin in multimodality treatment (MMT)

of rectal cancer – a single center experience

Beate Michels1; Torsten Liersch2; Johanna Kreutzer2; Timotheus Ritter2;

Andreas Leha3; Friederike Braulke4,5

1Universitätsmedizin Göttingen, Klinik für Gastroenterologie, gastrointestinale

Onkologie und Endokrinologie, Göttingen, Deutschland

2Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und

Kinderchirurgie, Göttingen, Deutschland

3Universitätsmedizin Göttingen, Institut für medizinische Statistik, Göttingen,

Deutschland

4Universitätsmedizin Göttingen, Universitätskrebszentrum Göttingen,

Onkologisches Zentrum, Göttingen, Deutschland

5Universitätsmedizin Göttingen, Klinik für Hämatologie und medizinische

Onkologie, Göttingen, Deutschland

Background: Use of oxaliplatin (OX) in MMT for locally advanced ade-

nocarcinoma of the rectum (LARC) combined with 5-FU-based chemo-

radiotherapy (CRT, 50.4 Gy), total mesorectal excision (TME) and pre-/

postoperative chemotherapy (CTx) is still under debate. Its role in total

neoadjuvant treatment (TNT) needs to be claried.

Methods: 177 LARC patients (cUICC stages II-IV in 4, 91 and 5.1%,

respectively; tumor height: <12 cm above anal verge) were treated between

7/2006 to 6/2016 at a single center according to clinical trial protocols

in cohorts A (preopCRT▶TME▶ 5-FU; n=64), B (preopCRT+5-FU+

OX▶TME▶ FOLFOX; n=63) and C (preopCRT+5-FU+OX▶3 appli-

cations of FOLFOX▶TME; n=50). Feasibility, toxicity, compliance, and

ecacy of MMT were analyzed. In addition, clinicopathological parame-

ters were assessed for prognostic relevance using COX regression analyses

and uni-/multivariable survival models.

Results: CRT resulted in > 98.1% (12.2% dose adherence); CTC-AE-

grades ≥3 at <4.5%; compliance at 98%; adCTx at 77% (28% dose reduc-

tion). Cohort C had the lowest rate of CTC-AE grade ≥3. In cohorts A and

B, adCTx was also associated with low rate of CTC-AE grade ≥3 toxicity

(<8%). Outcomes aer TME showed R0-status in 96%, negative CRM

in 92% (≥2 mm), and a reduction in longitudinal tumor extent of >50%

(ypTE: ≤25 mm). Histopathologic staging revealed stages ypUICC-0-IV

in 14.5, 23.1, 27.7, 24.9, and 9.6%, respectively. Distant and local recur-

rences occurred in 31.3 and 5.4% (median 73-m follow-up), respectively.

Univariate analyses showed dierences in DFS for MMT-induced tumor

regression (p=0.001), ypCRM (p=0.002), ypTE (p=0.023) and ypUICC

status (p< 0.0009). Multivariate analysis revealed higher CSS for ypUICC

stages ≤II (p=0.007; HR: 0.31; 95% CI: 0.14-0.73).

Discussion: In future, early available stage should be used to adjust adCTx

to individual recurrence risk. However, patients with stages ≤II aer TNT

do not require further adCTx.

Conclusion: OX in MMT is safe, feasible, and leads to improved early

tumor regression, esp. In TNT, associated with good compliance and

survival.

Disclosure Statement: e authors declare no conict of interest.

1037

Analysis of colorectal cancer and adenoma microbiome

signatures and the application of machine learning

classication as a potential screening tool

Katarina Priselac1; Christian Jansen2; Catia Pacíco2; Barbara Sladek2;

Nikolaus Gasche2

1Technische Universität Wien, Fakultät für Technische Chemie, Institut für

Verfahrenstechnik, Umwelttechnik und technische Biowissenschaften, Wien,

Österreich

2Biome Diagnostics GmbH, Wien, Österreich

Background: Recent studies have shown a link between the develop-

ment of colorectal cancer (CRC) & the composition of a patient’s intes-

tinal microbiome. Since this cancer usually progresses from an adenoma

form, detection at an initial adenoma stage is crucial for increasing the

success rate of treatment. is study aims to identify microbial signatures

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 75

associated with CRC & adenoma and to optimize machine learning (ML)

algorithms for stool based early screening of CRC.

Methods: Datasets containing amplicon sequencing information from

healthy individuals & adenoma/CRC patients were obtained from pub-

licly available repositories and merged into a single meta-analysis dataset

containing 1786 samples. Dierential abundance (DA) analysis has been

conducted using the MaAsLin2 package. ML models were built in Python

using the sckit-learn library.

Result: DA analysis of CRC vs. healthy samples resulted in a total of 44

dierentially abundant taxa (q<0.05, abs(coe) > 1.5), 8 of which were

increased in CRC stool samples. Comparison of adenoma & healthy

samples revealed enrichment of one taxon in adenoma samples. e

best ML performance for CRC-healthy classication was obtained using

a Support Vector Machine model resulting in an area under the curve

(AUC) of 0.84 on the cross-validation and 0.80 on the test dataset. For

the adenoma-healthy distinction, the Light Gradient Boosted Machine

model achieved an AUC of 0.85 on the cross-validation and 0.72 on the

test dataset.

Discussion: DA analysis results between CRC & healthy samples match

with reported ndings. For the rst time, a large meta-analysis dataset

has been used for CRC and adenoma predicting purposes using machine

learning algorithms.

Conclusion: Results demonstrate the suitability of ML algorithms for the

development of microbiome-based solutions for non-invasive screening

of CRC and colorectal adenomas. Future aspects include comprehensive

interpretation of the created models to nd a universal microbial bio-

marker for CRC and colorectal adenomas.

Disclosure Statement: e authors declare no conict of interest.

1045

Impact of BOLD-100 on glucose metabolism and protein

glycosylation: role in resistance against the ruthenium

complex

Theresa Mendrina1,2; Dina Baier1,2; Beatrix Schoenhacker-Alte1,2;

Christine Pirker2; Thomas Mohr2; Petra Heeter2;

Bernhard K. Keppler1; Walter Berger2

1Institute of Inorganic Chemistry, University of Vienna, Vienna, Österreich

2Center of Cancer Research and Comprehensive Cancer Center, Medical

University Vienna, Vienna, Österreich

Cellular energy metabolism is reprogrammed in cancer to fuel prolifer-

ation. Identifying metabolic changes as vulnerabilities might open novel

approaches for resistance prevention or targeting. Sodium trans-[tetra-

chlorobis(1H-indazole)ruthenate(III)] (BOLD-100), a ruthenium-based

metal complex currently evaluated clinically, exerts strong metabolic

activities. Data published recently by our group showed deregulation of

the carbohydrate metabolism as direct response to and resistance factor

against BOLD-100. In fact, enhanced glycolytic activity as metabolic vul-

nerability was identied in BOLD-100 resistance, suggesting targeting of

glycolysis as a promising strategy to promote BOLD-100 anticancer activ-

ity. However, detailed information about the impact of BOLD-100 on gly-

colysis downstream pathways, such as pentose phosphate pathway and/or

hexosamine biosynthetic pathway (HBP), is still incomplete.In this study,

the activity of those pathways was investigated in BOLD-100-sensitive

versus -resistant colon and urothelial cancer cells by using specic phar-

macologic inhibitors.Resistant cell models showed resensitisation towards

BOLD-100 when HBP was inhibited using glutamine-fructose-6-phos-

phate amidotransferase or O-GlcNAc transferase inhibitors. Fittingly,

gene set enrichment analysis (GSEA) of whole-genome gene expression

data indicated signicant enrichment of the term “O-Glycan biosynthe-

sis” in resistant compared to parental cells. Especially, the rst enzyme

of O-glycosylation, N-acetylgalactosaminyltransferase, was upregulated

during acquisition of BOLD-100 resistance. Accordingly, this gene set was

signicantly downregulated in parental cells upon BOLD-100 treatment.

Currently, we concentrate on the impact of glycosylation on the mode of

action of BOLD-100 and vice versa, focusing on glycosylation of GRP78,

a known target of BOLD-100. In summary, targeting O-glycosylation rep-

resents a potential new approach to circumvent BOLD-100 resistance.

Disclosure Statement: e authors declare no conict of interest.

1069

Role of magnetic resonance imaging (MRI) in upper rectal

cancer (≥12 cm above anal verge, AV) – a single-center

experience

Andreas Leha1; Ali Seif2; Johanna Kreutzer3; Laura Werle3;

Timotheus Ritter3; Carsten-Oliver Sahlmann4; Torsten Liersch3

1Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,

Deutschland

2Institut für Diagnostische und Interventionelle Radiologie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

3Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

4Klinik für Nuklearmedizin, Universitätsmedizin Göttingen, Göttingen,

Deutschland

Background: Pelvic MRI is well established in staging of advanced cancer

(stages ≥II) in the lower parts of the rectum (<12 cm above AV). In upper

rectal cancer (≥12 cm), its value is still unclear.

Methods: In this single-center project, staging with MRI, rES, and CT

was compared with outcomes aer upfront surgery (TME vs. PME) in 98

participants of the GAST-05 phase II trial (ISRCTN35198481). MRI accu-

racy (mrAC) was determined based on cancer stage (7th TNM/UICC-

classication). Parameters such as T, N, and UICC status, circumferential

resection margin (CRM), extramural vascular inltration (EMVI) were

analyzed for recurrence-free survival (RFS) using logrank test, Kaplan-

Meier estimator, and multiparametric Cox proportional hazard regression

models. MRI evaluations (MRI 2nd read) of tumor site, peritoneal reection

fold (PRF), and mrEMVI were then performed in 35 patients.

Results: Postsurgical staging revealed stages I to IV in 14.3, 43.9, 36.7 and

5.1%, respectively. mrAC was 79.3% for distinguishing stages ≥II vs. <II

and 74.5% and 85.1% for N status and stage (≥II), respectively (vs. 59.6%

and 72.3% with rES). In addition, MRI was superior to rES and CT in

describing CRM and EMVI. Using survival models in cohort A (n=47;

with MRI) vs. B (n=51; without MRI), patients age, stage ≥III, and T

status were shown to have signicant impact on RFS. MRI 2nd read revealed

that the PRF was signicantly closer to the AV and the aboral tumor mar-

gin was more distant in women (median 40 mm vs. 12.5 mm). mrAC in

EMVI was 48.6%, but the postulated positive mrEMVI (82.9%) was con-

rmed as positive pL-/V-/Pn status in only 11 specimens (31.4%). Patients

with a negative pL-/V-/Pn status had better CSS.

Discussion: Considering the surgical-anatomical landmarks, MRI staging

in upper rectal cancer could facilitate the decision for a more individual-

ized treatment.

Conclusion: Staging MRI combined with rES and rigid rectoscopy should

be used in patients with cancer in the upper rectum (≥12 cm) and recto-

sigmoid (>16 cm to 30 cm) to optimize preoperative assessment of T, N,

UICC, CRM, EMVI status and tumor location.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts76

1071

Adjuvant FOLFOX (adCTx) in cancer of the upper rectum (≥12

cm above AV) after upfront surgery – single-center experience

Charlotte de Boer1; Andreas Leha2; Julie Schanz3; Beate Michels4;

Johanna Kreutzer1; Timotheus Ritter1; Torsten Liersch1

1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen,

Göttingen, Deutschland

2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,

Deutschland

3Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

4Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie,

Universitätsmedizin Göttingen, Göttingen, Deutschland

Purpose: To evaluate safety, feasibility and ecacy of FOLFOX in cancer

of the upper rectum (stages II and III, ≥12 cm) aer total (TME) vs. par-

tial (PME) mesorectal excision.

Methods: Upfront surgery was performed in 98 (median age: 69) partici-

pants of the GAST-05 phase II trial (ISRCTN35198481). Aer conrma-

tion of stage II or III (7th TNM/UICC-classication) 4 cycles of FOLFOX

(FA: 400 mg/m²; 5-FU: 2400 mg/m²; OX: 100 mg/m²) were indicated.

Acute and late toxicities were determined according NCI-CTCAE criteria

(v3.0). Survival was calculated using the logrank test, Kaplan-Meier esti-

mator, and multiparametric Cox proportional hazard regression models.

Results: Upfront surgery quality was good, moderate or poor quality

in 82.7, 16.3 and 1%, respectively. Advanced disease had to be stated in

>50%, due to pT4a/b (13.3%) or pN1/N2 status (42.9%). AdCTx was

started in 62 patients; 96.6% of planned cycles could be administered, and

5-FU and OX doses were 90.8% and 73.4% of target. During adCTx, 772

AEs were reported with hematologic (n=205), gastrointestinal (n=221)

and neurologic (n=151) AEs clustered; CTCAE-grade 3/4 occurred in

3.5%. During follow-up (median: 101 months), 386 late AEs were noted,

with 11.1% having grade 3/4. Neurotoxicity accounted for 24.4% (17.0%

grade 2) and diarrhea for 34.7% (18.4% grade 3/4). Together with fecal

incontinence (12.7%), 47.4% of all late events were due to defecation dis-

orders. Low anterior resection syndrome was present in 44.1% and more

frequent aer TME (p=0.007). Aer adCTx, the 3- and 5-year OS was

87.1% and 82.3%, respectively, vs. 75.0% and 68.8% (without adCTx).

Stage III patients had better DFS (p=0.058); 3- and 5-year DFS were

68.8% and 65.6%, respectively, vs. 40.0%. OS was also prolonged in stage

III (p=0.003); the 3- and 5-year OS was 81.3% and 78.1%, respectively

(vs. 40.0% without adCTx).

Discussion: is study contributes to the debate on optimal therapy for

upper rectal cancer. Stage II patients also appear to have a survival benet

with adCTx.

Conclusions: mFOLFOX improves survival in patients with stage III

upper rectal cancer.

Disclosure Statement: e authors declare no conict of interest.

1073

Preoperative chemoradiotherapy (preopCRT) for locally

advanced rectal cancer (LARC) - a benet for all? - the view

of a study site

Recca Talaulicar1; Andreas Leha2; Julie Schanz3; Johanna Kreutzer1;

Timotheus Ritter1; Tatiana Grammatikopoulou1; Torsten Liersch1

1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,

Deutschland

3Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

Purpose: To evaluate ecacy of 5-FU-based preopCRT±OX followed by

total mesorectal excision and adjuvant CTx vs. upfront surgery for LARC

(<16 cm above anal verge).

Methods: 402 LARC patients (median age: 64 yrs) were treated between 1998

to 2013 in the CAO/ARO/AIO-94, -04 and GAST-05 (ISRCTN35198481)

trials. e ecacy of therapy was assessed by logrank test, Kaplan-Meier

estimator and univariable survival models. Multivariable proportional

Cox regression models were tted for risk factors and survival endpoints,

adjusting for risk factor, pretreatment, tumor location, and their 2-way

interactions, and treatment regimen.

Results: Aer upfront surgery (n=180), stages I to IV were diagnosed in

13.9, 40.0, 41.7, and 4.4%, respectively. Aer preopCRT (n=222), stages

0 to IV were detected in 14.9, 19.4, 33.6, 33.1, and 5.7%, respectively.

During 91m follow-up (median), 119 recurrences occurred in 30.0%;

local recurrences had been detected in 1% (alone) and 5.3% (together with

distant metastases). Paired contrast tests for OS showed that preopCRT

favored stages ≤II (HR: 0.37; p<0.001). Similarly, preopCRT showed a

positive eect for stages ≤II in the upper rectum (HR: 0.16; p = 0.004).

is eect appears to be synergistic, as OS was also better aer upfront

surgery in stages ≤II vs. >II (HR: 0.37; p = 0.018). For DFS, there was

a similar eect of preopCRT in favor of stages ≤II (HR: 0.37; p<0.001).

In CSS, preopCRT was in favor of stages ≤II (HR: 0.22; p<0.001) in the

lower and mid rectum and for carcinomas in the upper third (HR: 0.0096;

p=0.001). In this tumor location, patients with stages ≤II vs. >II per se

had better CSS (HR: 0.029; p = 0.007); thus, the actual benet of preop-

CRT remains questionable.

Discussion: In stage ≤II upper rectal cancer, there was no patient dis-

advantage when preopCRT was omitted. Whether patients with stage III

aer upfront surgery benet from more intensive adCTx (vs. FOLFOX)

should be assessed in clinical trials.

Conclusion: PreopCRT+OX resulted in better survival in stage ≤II cancer

(<12 cm above AV), and stages >II were identied as «non-responders».

Disclosure Statement: e authors declare no conict of interest.

1075

Peri-/postoperative quality control in locally advanced rectal

cancer (LARC) after preoperative multimodal treatment

(MMT) or upfront surgery– any evidence on survival?

Tatiana Grammatikopoulou1; Andreas Leha2; Julie Schanz3;

Johanna Kreutzer1; Laura Werle1; Charlotte de Boer1; Torsten Liersch1

1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,

Deutschland

3Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

Purpose: To evaluate the role of peri-/postoperative control and clinico-

pathological risk factors in specimen aer total (TME) or partial (PME)

mesorectal excision in ≥stage II rectal cancer (≤16 cm above anal verge)

treated with preoperative, 5-FU-based chemoradiotherapy (preop-

CRT)±Oxaliplatin (OX) or upfront surgery.

Methods: 402 participants of the CAO/ARO/AIO-94, -04 and GAST-05

(ISRCTN35198481) trials with stage ≥II rectal cancer were included in

this project at a single study site. Standardized peri-/postoperative qual-

ity control of the specimen and extended histopathological work-up was

performed according to trial protocols, MERCURY criteria, and the 7th

TNM-/UICC-classication. e impact of selected prognostic parameters

on survival was investigated by using Logrank test, Kaplan-Meier estima-

tor, uni-/multiparametric Cox proportional hazard regression models,

and interaction eects testing models.

Results: Optimal quality of TME/PME-surgery was demonstrated peri-

and postoperatively in 80.4% and 78.7% of specimen, respectively. e

rate of optimal resections aer preopCRT+OX was increased to 82.5%

and 77.8%, respectively, compared with 76.6% and 70.3% for MMT with-

out OX. In patients with LARC in the lower rectum (<12 cm) treated

with preopCRT who had positive pCRM status, there was a benet in DFS

(HR: 5.9; adjusted p=0.002). Aer preopCRT, negative nodal status (N0)

showed better DFS for LARC in the lower and mid thirds of the rectum

(ypN0 status; HR: 0.41, p<0.001) and in the upper third aer upfront sur-

gery (pN0 status; HR: 0.44; p=0.003) and aer preopCRT (ypN0 status;

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 77

HR: 0.25, p=0.003). Further data from multivariable survival models will

be presented at DKK 2022.

Discussion: Standardized peri/postoperative control of rectal cancer

surgery provides signicant improvement in specimen quality and more

accurate cancer staging.

Conclusion: Based on high-quality surgery, preoperative CRT synergisti-

cally improves survival in intermediate and lower rectal cancer (<12 cm)

and opens the door for risk-adapted adjuvant treatment.

Disclosure Statement: e authors declare no conict of interest.

1077

MRI (1.5T) monitoring as early predictor of survival in

advanced rectal cancer during preoperative multimodal

treatment (MMT)

Torsten Liersch1,1; Ali Seif Amir Hosseini2; Timotheus Ritter1;

Carsten-Olive Sahlmann3; Johanna Kreutzer1; Leif Hendrik Dröge4;

Julia Kitz5; Andreas Leha6

1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen;

Göttingen, Deutschland

2Institut für Diagnostische und Interventionelle Radiologie, Universitätsmedizin

Göttingen, Göttingen, Deutschland

3Klinik für Nuklearmedizin, Universitätsmedizin Göttingen, Göttingen, Deutschland;

4Klinik für Strahlentherapie und Radioonkologie, Universitätsmedizin Göttingen,

Göttingen, Deutschland

5Institut für Pathologie, Universitätsmedizin Göttingen, Göttingen, Deutschland

6Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,

Deutschland

Background: Baseline 1.5 Tesla MRI (MRI-I) is standard for locally

advanced rectal cancer (LARC) to indicate preoperative 5-FU-based

chemoradiotherapy (preopCRT). e prognostic signicance of pre-sur-

gical MRI-II (in dierence (Δ) to MRI-I) is controversial.

Methods: In this monocentric posthoc-study, 125 patients (47 f, 78 m;

median age: 68 years) with LARC (clinical stages II to IV in 5.6%, 92.0%,

and 2.4%, respectively) received preopCRT ± Oxaliplatin followed by

TME-surgery. Imaging and post-surgical parameters were tested for asso-

ciation with recurrence-free (RFS), overall (OS) and cancer-specic (CSS)

survival. ree multiple Cox regression models were built using grouped

lasso penalization: (1) pre-surgical (imaging), (2) post-surgical (patholog-

ical) and (3) post-treatment (all variables). Patients were classied in high-

or low-risk survivors in a 10-fold cross validation (CV). e post-surgical

models were extended with additionally informative imaging parameters

as conrmed by likelihood ratio tests.

Results: Post-surgical staging revealed (yp)stages 0 to IV in 13.6%, 28.0%,

25.6%, 23.2% and 9.6%, respectively. Restricted mean for RFS, OS and

CSS were 88.9±5.5, 100.4±4.9 and 119.4±4.7 months. Survival rates

aer 2.5, 5 and 7.5 years amounted to 68.8%, 59.9%, 56.4% for RFS; to

84.8%, 68.7%, 60.3% for OS, and to 89%, 80% and 73% for CSS, respec-

tively. In the pre-surgical models increased hazard ratios (HR) for RFS

were observed in MRI-I_Δ_MRI-II T status (p=0.01) and MRI-I_Δ_

MRI-II TE (longitudinal tumor extent) (p=0.04). Increased HR for OS

was seen in MRI-I_Δ_MRI-II TE (p=0.02). CV of the pre-surgical risk

models dierentiated survivors in RFS (p=0.019) and OS (p<0.001).

Discussion: MRI monitoring is useful for early prediction of survival in

advanced rectal cancer

Conclusion: Our ndings strongly suggest MRI as easily available

pre-surgical tool for early adjustment of (multimodal) treatment.

Disclosure Statement: e authors declare no conict of interest.

Gastrointestinal (Non-colorectal) Cancer

Best-of-Abstract-Vortrag

1005

Real-World Use of PARP inhibitors in BRCA1/2-Mutated

Pancreatic Cancer: A Retrospective Analysis

Danmei Zhang1; Suvina Amin2; Weiyan LI2; Seongjung Joo3;

Gboyega Adeboyeje3; Patricia Dearbeloa4; Emanuel F Petricoin III4,5;

Edik M Blais4; Michael J Pishvaian4,6

1Klinikum Großhadern, Medizinische Klinik und Poliklinik III, München,

Deutschland

2AstraZeneca, Gaithersburg, USA

3Merck, Kenilworth, USA

4Perthera Inc., Holliston, MA , USA

5George Mason University, Fairfax, USA

6Johns Hopkins School of Medicine, Baltimore, USA

Background: Olaparib is the only PARP inhibitor (PARPi) approved in the

EU and the US as maintenance treatment for biomarker-selected patients

with mPaC in the 1st line platinum-sensitive setting. However, treatment

sequencing can be heterogeneous, and there is a lack of real-world data on

patterns of PARPi use in relation to platinum use in BRCA1/2-mutated

mPaC.

Methods: Longitudinal records collected between 1/2012-12/2020 were

analyzed for a cohort of 55 mPaC patients with BRCA1 or BRCA2 muta-

tions identied by commercial NGS testing who enrolled in Perthera’s

US real-world observational registry study. Treatment patterns including

PARPi utilization and platinum-sensitivity (16 weeks without progression

at any point within known history) were abstracted via physician notes

across all lines of therapy.

Result: PARPi use was documented in 60% (N=33) of 55 patients with

BRCA1/2-mutated mPaC in any treatment setting. Within this cohort,

21 patients received a single agent PARPi outside of clinical trials.

Among these patients, only 38% (8 of 21) transitioned to a PARPi in a

platinum-sensitive context, and only 14% (3 of 21) of these transitions

occurred before 2nd line. Notably, 6 patients received a PARPi in the plat-

inum-resistant setting. Within the broader cohort, platinum-sensitive

criteria was fully met for 73% (40 of 55); however, only 49% (27 of 55)

reached this milestone of platinum-sensitivity prior to initiating a 2nd line

therapy.

Conclusion: e majority of these BRCA1/2-mutated patients received

a PARPi-based therapy in a variety of contexts with respect to line of

therapy and prior platinum history. ese ndings highlight the value of

upfront genetic and molecular testing and the need for further exploration

to identify factors associated with treatment response as well as optimized

treatment sequencing.

Indication of source:

1 American Society of Clinical Oncology Gastrointestinal Cancer Symposium,

Jan 20-22, 2022

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts78

Poster

Distance matters: Correlation of HCC nodule distance to

overall survival

Yuquan Qian1; Baojiang Liu2; Christel Weiss3; Xu Zhu2; Andreas Teufel1,4,5

1Heidelberg University, Medical Faculty Mannheim, University Medical Center

Mannheim, Department of Medicine II, Mannheim, Deutschland

2Peking University Cancer Hospital and Institute, Key Laboratory of

Carcinogenesis and Translational Research (Ministry of Education), Department

of Interventional Therapy, Beijing, China, VR

3Heidelberg University, Medical Faculty Mannheim, Heinrich Lanz Center for

Digital Health, Department of Statistics, Biomathematics and Information

Processing, Mannheim, Deutschland

4Heidelberg University, Medical Faculty Mannheim, University Medical Center

Mannheim, Department of Medicine II, Division of Hepatology, Division of

Bioinformatics, Mannheim, Deutschland

5Heidelberg University, Medical Faculty Mannheim, Center for Preventive

Medicine and Digital Health Baden-Württemberg (CPDBW), Clinical Cooperation

Unit Healthy Metabolism, Mannheim, Deutschland

Background: Hepatocellular carcinoma (HCC) may occur with several

simultaneous tumor foci in the liver (multifocal HCC). Molecular biol-

ogy indicated that the larger the distance between two tumor nodules, the

more those two nodules diered in their genetic composition. erefore,

we explored whether the overall survival of patients with HCC depends

on the mutual distance of the HCC nodules.

Methods: In a retrospective study of 92 patients, CT/MRI images and sur-

vival data of the patients were collected. Based on the CT or MRI images

at the time of diagnosis, the size of each tumor, the distance between the

centers (center distance) and adjacent edges (edge distance) of the tumor

nodules were measured respectively. ese data, combined with the num-

ber of tumor nodules and clinical characteristics, were compared with the

patient’s overall survival data.

Result: As expected, the average tumor diameter was signicantly associ-

ated with patient survival in univariate cox regression analysis (p=0.00028,

HR=1.2). However, in multivariate analysis, the average center distance

(p=0.036, HR=1.18) and average edge distance (p=0.033, HR=0.84) were

also signicantly associated with survival.

Discussion: Our data provided new insight into assessing the survival of

multifocal HCC patients. We showed that the distance between tumor

nodules is a potential predictor of the overall survival of patients with

multifocal HCC, which may be due to the fact that distance is related to

rapid biological evolution and multiple molecular alterations.

Conclusion: Not only the size of multiple HCC lesions but also their dis-

tance is important for the prognosis of patients with HCC. is may be of

particular interest in patients with two nodules and BCLC B and C stages

for the selection of therapeutic modalities and/or procedures.

Indication of source (Optional, bitte löschen Sie diesen Absatz, wenn Sie

keine Quellenangaben haben):

Indication of source:

1 is project was also submitted to e Liver Meeting 2021

Disclosure Statement: e authors declare the following: Prof. Teufel is supervisor

of Yuquan Qian for doctoral study.

IMbrave150: exploratory ecacy and safety results of

atezolizumab + bevacizumab vs sorafenib in patients (pts)

with unresectable hepatocellular carcinoma (HCC) who had

prior locoregional therapy (LRT)

Peter R. Galle1; Riad Salem2; Richard S. Finn3; Michel Ducreux4;

Amit G. Singal5; Alan Nicholas6; Sairy Hernandez6; Wendy Verret6;

Philippe Merle7; Andrew X. Zhu8,9

1I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz,

Deutschland

2Northwestern University, Chicago, USA

3Jonsson Comprehensive Cancer Center, Geen School of Medicine at UCLA, Los

Angeles, , Los Angeles, USA

4Gustave Roussy Cancer Center, Villejuif, Frankreich

5UT Southwestern Medical Center, Dallas, USA

6Genentech Inc., South San Francisco, USA

7University Hospital La Croix-Rousse, Lyon, Frankreich

8Massachusetts General Hospital Cancer Center, Harvard Medical School,

Boston, USA

9Jiahui International Cancer Center, Shanghai, China, VR

Background: Atezolizumab (atezo) + bevacizumab (bev) has been

approved in > 70 countries for systemic treatment (tx)–naive pts with

unresectable HCC, based on IMbrave150 (NCT03434379¸ Finn RS

NEJM 2020). Here, we report post hoc exploratory results of atezo + bev

vs sorafenib (sor) in pts who had prior LRT using updated data with 12

months of further follow-up from primary analysis.

Methods: Pts were randomised 2:1 to atezo 1200 mg IV q3w + bev 15 mg/

kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical

benet per investigator. IMbrave150 enrolled 501 systemic tx–naive pts

with unresectable HCC, ≥ 1 measurable untreated lesion (RECIST 1.1),

Child-Pugh class A liver function and ECOG PS ≤1, including pts with

prior LRT.

Result: 175, 84, 77 atezo + bev and 80, 44, 41 sor pts had 0, 1-2 and ≥ 3

prior lines of LRT, respectively. Compared with sor, atezo + bev pts had

median overall survival (mOS) of 19.4 vs 13.1 mo (HR, 0.61; 95% CI: 0.44,

0.86) in pts without prior LRT, 22.8 vs 10.2 mo (HR, 0.60; 95% CI: 0.36,

1.00) in pts with 1-2 LRTs and 17.4 vs 16.6 mo (HR, 0.83; 95% CI: 0.51,

1.37) in pts with ≥ 3 LRTs.

In the three LRT-subgroups (0, 1-2, ≥ 3 prior lines), median progres-

sion-free survival in atezo + bev pts was 6.7 / 9.4 / 6.7 months, vs 4.8 /

4.0 / 4.4 months in sor pts. e objective response rates were 29 / 35 / 25

% in the atezo + bev subgroups, and 15 / 5 / 10 % in the sor subgroups. A

complete response occurred in 5 %, 14 % and 8 % in atezo + bev pts, but in

only one of 159 evaluable sor pts. Stable disease was documented in 39-49

% in the atezo + bev subgroups, and in 37-53% in sor pts.

Grade 3-4 treatment-related adverse events were seen in 79 (46%), 33

(39%) and 31 (41%) atezo + bev pts and 30 (39%), 20 (49%) and 22 (58%)

sor pts who had 0, 1-2 and ≥ 3 LRTs, respectively.

Conclusion: Survival benet with Atezolizumab + Bevacizumab over

Sorafenib was seen in patients regardless of the number of prior LRTs.

Atezolizumab + Bevacizumab seemed to have more benet in patients

with 1-2 vs ≥ 3 prior LRTs, suggesting an optimal time for switching from

LRT to systemic therapy.

Disclosure Statement: e authors declare the following: Honoraria -

Adaptimmune; Bayer Schering Pharma; Bristol-Myers Squibb; Ipsen; Lilly; MSD;

Roche/Genentech; Sirtex Medical Consulting or Advisory Role - Adaptimmune;

Bayer Schering Pharma; Bristol-Myers Squibb; Lilly; MSD; Roche/Genentech;

Sirtex Medical Speakers’ Bureau - Bayer Schering Pharma; Ipsen; Lilly; Roche

Travel, Accommodations, Expenses- Bayer Schering Pharma; Lilly; Sirtex Medical

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 79

N-CROSS neoadjuvant chemoradiotherapy of the esophageal

cancer at the Nuremberg Hospital North

Thomas Gryc1; Christian Grehn1; Irina Bosancu1; Cansu Cabuk1;

Martin Wilhelm2; Marcus Seifert2; Attila Dubecz3; Wolfgang Brückl2;

Hubert Stein3; Clemens Albrecht1

1Nürnberg, Praxis für Strahlentherapie Nordstrahl, Nürnberg, Deutschland

2Paracelsus Medizinische Privatuniversität , Klinikum Nürnberg, Innere Medizin,

Nürnberg, Deutschland

3Paracelsus Medizinische Privatuniversität, Klinikum Nürnberg, Chirurgie,

Nürnberg, Deutschland

Background: We conducted an assessment of eectivity for our multi-

modal treatment schedule of loco regionally advanced esophageal cancer.

Methods: Patientdata treated for locally advanced esophageal cancer or

cancer of the gastroesophageal junction between 01/2015 and 09/2020

was analyzed. Patients were treated in analogy to the CROSS-protocol.

Alternatively, a chemoradiotherapy (RCT) with simultaneous 5-uo-

rouacil with a platinum compound was applied. Aer an interval of 2.1

months, surgery including a two-eld lymphadenectomy was performed.

Results: Of the 49 patients evaluated, 83.7 % were male. Histological

workup revealed 61.2 % adenocarcinoma (AC) and 38.2 % squamous

cell carcinoma (SCC). 33.3 % of the SCC tumors and 27.8 % of the AC

received a treatment in analogy to the CROSS- protocol and the remain-

ing received a RCT of 45 Gy and 5-uorouacil/platinum. A pathological

complete remission was achieved in 26.5 % and in additional 36.7% less

than 10% vital tumor cells were detected in the tumor bed aer neoad-

juvant treatment (Becker tumor regression grade IB). us, neoadjuvant

RCT resulted in grade I regression in a total of 63.2%. R0 resection was

achieved in 100% of the patients. 2-year overall survival was 80% inde-

pendently of tumor histology (p=0.325) or the neoadjuvant treatment

(p=0.923). Median disease free survival (DFS) was 7.3 months and was

shorter for AC than for SCC (p=0.021). In case of a pathologic response

>90% the disease free survival was signicantly improved to 12.8 months

(p=0.034). For SCC tumors treated with CROSS, DFS was prolonged. Still,

in general DFS did not dier between CROSS-protocol and the 5-uo-

rouacil/platinum based therapy (p=0.436).

Conclusion: Our data demonstrate the good feasibility of multimodal

therapeutic regimen in clinical routine in the context of close interdis-

ciplinary collaboration. Emphasis should be paid to individual adapta-

tion of the therapy regimen to the tumor specications. In particular, the

degree of pathologic response to neoadjuvant treatment exerts a signi-

cant inuence on clinical outcome.

Disclosure Statement: e authors declare no conict of interest.

Long-term survival of a patient with metastatic and recurrent

pancreatic acinar cell carcinoma harboring somatic BRCA1/2

variants of unknown signicance treated with Olaparib

maintenance therapy following local treatment

Christian Müller1; Sabine Franke2; Maciej Janusz Powerski3;

Thomas Brunner4; Marino Venerito1

1Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie,

Otto-von-Guericke Universitätsklinikum, Magdeburg, Deutschland

2Institut für Pathologie, Otto-von-Guericke Universitätsklinikum, Magdeburg,

Deutschland

3Universitätsklinik für Radiologie und Nuklearmedizin, Otto-von-Guericke

Universitätsklinikum, Magdeburg, Deutschland

4Universitätsklinik für Strahlentherapie, Otto-von-Guericke Universitätsklinikum,

Magdeburg, Deutschland

Background: Acinar cell carcinoma of the pancreas (PACC) is a rare

malignant disease oen with an advanced or metastatic stage at initial

diagnosis. ere are no standardized therapy recommendations for the

treatment of non-resectable disease.

Methods: Here we present a case of a patient with a PACC who has shown

a sustained response to multimodal therapy (chemotherapy, local treat-

ment and targeted therapy).

Result: In 2017, a 61-year-old man presented with persistent back pain.

Initial imaging revealed a hypodense lesion in the pancreatic corpus and

both lobes of the liver. Histological examination of a hepatic lesion con-

rmed the diagnosis of PACC. He received a 12 cycles FOLFIRINOX

achieving partial remission, followed by FOLFIRI maintenance therapy

(15 cycles). Aer 22 months, a progressive disease was documented.

Gemcitabine/nab-paclitaxel failed to stop progression. us, the patient

received Stereotactic Body Radiation erapy of the primary tumor and

transarterial radioembolisation of the liver metastases. e mutation anal-

ysis of the tumor biopsy revealed mutations with unknown signicance

in both BRCA1 (c.800C>T) and BRCA2 (c224C>T). Maintenance treat-

ment with the PARP inhibitor Olaparib induced disease control over 12

months, despite an early dose reduction due to neutropenia and thrombo-

cytopenia. ereaer, a documented progression of liver metastases was

controlled with transarterial chemoembolization. Olaparib maintenance

therapy was kept until disease progression in April 2022. Overall, with this

approach the patient is still alive aer 61 months.

Discussion: In our patient, Olaparib maintenance therapy may have

contributed to disease control aer local treatment. Further studies are

needed to conrm a pathogenic role for the BRCA1 c.800C>T and BRCA2

c224C>T somatic variants.

Conclusion: In our patient with a chemo-resistant PACC, harboring

somatic BRCA1/2 variants of unknown signicance, Olaparib mainte-

nance therapy following local ablative procedures was feasible and con-

tributed to an excellent survival benet.

Disclosure Statement: e authors declare no conict of interest.

179

Inuence of the hepatic microenvironment on the migration

behavior of premalignant and malignant pancreatic ductal

epithelial cells

Svenja Quaester1, Silje Beckinger1, Tina Daunke1, Lisa-Marie Philipp1,

Claudia Seemann1, Sascha Rahn2, Susanne Sebens1

1Institut für Experimentelle Tumorforschung, Christian-Albrechts-Universität zu

Kiel, Kiel, Deutschland

2Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, Kiel,

Deutschland

Background: e poor prognosis of patients with pancreatic ductal ade-

nocarcinoma is ascribed to diagnosis in advanced stages, pronounced

therapy resistance and high recurrence rates, the latter oen associated

with liver metastases. In order to develop eective therapeutic options,

a better understanding of the underlying processes of metastasis and the

involved Epithelial-Mesenchymal-Transition (EMT) is essential. us, the

present study investigated the impact of the hepatic microenvironment on

EMT and migration behavior of pancreatic ductal epithelial cells (PDEC).

Methods: Premalignant (H6c7-Kras) and malignant (PancTu1) PDEC

were indirectly cocultured with hepatic stellate cells (HSC) or hepatic

myobroblasts (HMF), mimicking a physiological or inamed hepatic

microenvironment. Aer 5 days, PDEC proliferation was assessed by cell

counting, EMT gene and protein expression were analyzed via PCR and

Western Blot and migration was examined performing wound healing

assays.

Result: Both proliferation rates and expression of EMT inducing fac-

tors were increased in PDEC by coculture with HMF compared to HSC.

Accordingly, E-cadherin expression was higher in both PDEC lines under

HSC compared to HMF coculture, with PancTu1 cells showing higher

basal expression levels than H6c7-Kras cells. In line, H6c7-Kras cells

migrated faster than PancTu1 cells, however, HSC coculture led to faster

wound closure compared to HMF coculture, in both cell lines.

Discussion: Overall these data suggest that a physiological hepatic

microenvironment reduces proliferation and E-cadherin expression

but supports migratory abilities in PDEC. In contrast, an inamed liver

micromilieu promotes a PDEC phenotype characterized by enhanced

proliferation and E-Cadherin expression but reduced cell migration.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts80

Conclusion: e hepatic microenvironment impacts cell proliferation

and EMT associated properties in premalignant and malignant PDEC in

dependence on the inammatory status.

Disclosure Statement: e authors declare no conict of interest.

211

First results from the prospective national intersectoral cohort

study JADE to assess characteristics, treatment and outcome

of patients with hepatocellular or cholangiocellular carcinoma

In Germany

Robert Thimme1; Jan Schröder2; Jens Uhlig3; Jens Freiberg-Richter4;

Matthias Zingerle5; Anke Schlenska-Lange6; Christiane Hering-Schubert7;

Fee Bengsch8; Larissa Elisabeth Hillebrand8; Hans Ulrich Siebenbach8;

Martina Jänicke8; Wolf Peter Hofmann9; Philippe Pereira10; Thomas Berg11;

Peter Galle12

1Universitätsklinikum Freiburg, Freiburg i. Br., Deutschland

2Praxis für Hämatologie, Onkologie, Palliativmedizin, Mülheim an der Ruhr,

3Onkologie Muldental, Naunhof

4BAG / Onkologische Gemeinschaftspraxis, Dresden, Deutschland

5Hämato-Onkologische Überörtliche Gemeinschaftspraxis Pasing und

Fürstenfeldbruck, München, Deutschland

6Krankenhaus Barmherzige Brüder, Regensburg

7St. Georg Klinikum, Eisenach, Deutschland

8iOMEDICO, Freiburg i. Br., Deutschland

9MVZ für Gastroenterologie am Bayerischen Platz, Berlin, Deutschland

10SLK-Kliniken , Heilbronn, Deutschland

11Universitätsklinikum Leipzig, Leipzig, Deutschland

12Universitätsmedizin Mainz, Mainz, Deutschland

Background: Hepatocellular carcinoma (HCC) and intrahepatic

cholangiocarcinoma (iCC) are the most common types of primary liver

cancer. Prospective real-world evidence of patients (pts) with liver cancer,

however, is still scarce.

Methods: JADE is a prospective, multicenter, intersectoral, longitudinal

cohort study that will collect data of up to 1,000 pts with HCC or CCC

from approximately 100 sites (clinics and oce-based) in Germany. Since

August 2020, pts with early, intermediate or advanced/metastatic stage

HCC or CCC are enrolled at start of local or systemic treatment. Data

are collected in electronic case report forms. Pts and tumor characteris-

tics, treatment and clinical and patient-reported outcome data are docu-

mented. In addition, pts can consent to the use of their routinely collected

tumor samples in future translational research.

JADE (NCT04510740) was approved by local ethics.

Result: At rst annual data base cut (2021-APR-30), 167 pts had been

recruited at 55 sites. Here, rst results are presented for pts with advanced

disease. Updated results (data base cut 2022-APR-30) will be shown at

the congress.

e 21 pts with advanced HCC (71% male) had a median age of 71 years,

81% had comorbidities and most pts were in rather impaired overall

condition (ECOG 0: 38%). e most frequently used 1L treatments were

atezolizumab+bevacizumab (n=13, 65%), and lenvatinib (n=4, 20%).

e 38 pts with advanced CCC (56% male) had a median age of 70 years,

84% had comorbidities and most pts were in quite fair condition (ECOG

0: 50%). In most pts (n=35), gemcitabine was applied in 1L treatment

(most frequently as gemcitabine+cisplatin (n=31, 82%).

Conclusion: JADE will, for the rst time, present real-world data on pts

and tumor characteristics, treatment and outcomes of pts with liver and

biliary tract cancer across all health care sectors in Germany. In the future,

JADE will shed light on the treatment landscape in real-world and will

help to identify unmet medical needs for future clinical research.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

259

Outcomes of patients with locally advanced or metastatic

pancreatic cancer treated with dierent sequential treatment

strategies –data from the prospective Tumour Registry

Pancreatic Cancer

Susanna Hegewisch-Becker1; Marcel Reiser2; Steen Dörfel3;

Christian Lerchenmüller4; Hartmut Linde5; Thomas Wolf6;

AdrianBinninger7; Natalie Wetzel7; Martina Jänicke7; Norbert Marschner8

1Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Hamburg, Deutschland

2PIOH - Praxis Internistische Onkologie und Hämatologie, Köln, Deutschland

3Onkozentrum Dresden/Freiberg, Dresden, Deutschland

4Hämatologisch-onkologische Gemeinschaftspraxis, Münster, Deutschland

5MVZ für Blut- und Krebserkrankungen, Potsdam, Deutschland

6BAG / Onkologische Gemeinschaftspraxis, Dresden, Deutschland

7iOMEDICO, Freiburg i.Br., Deutschland

8Praxis für Interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br., Deutschland

Background: FOLFIRINOX (FFX) and gemcitabine (GEM) + nab-pacl-

itaxel (GnP) are the two most active 1st-line treatment (1L) options and

standard of care for patients (pts) with locally advanced or metastatic

pancreatic cancer (mPC) and good performance status. Intense eorts are

ongoing to establish an optimized sequential treatment strategy that oers

improved survival but clinical trials on sequential treatments are miss-

ing. e clinical registry TPK provides detailed insight into longitudinal

treatment data and outcomes of pts with mPC treated in routine clinical

practice in Germany.

Methods: TPK is a prospective, multicenter, cohort study of pts with mPC

receiving systemic therapy. Since 2014, >2000 pts from 120 sites across

Germany were registered prior to start of 1L. Detailed data on patient

and tumor characteristics, treatment and outcome are recorded. Herein,

outcomes based on treatment sequences were evaluated. Progression-free

survival 2 (PFS2) was dened as time from start of 1L until rst progres-

sion aer start of 2nd-line (2L) treatment or death from any cause.

Result: Between 2014 and 2021, a total of 482 pts with mPC received

at least two lines of treatment. ereof, 228 pts received FFX>GnP, 101

pts GnP>FOLFOX/OFF, 74 pts GnP>nal-IRI+5-FU (NALIRI) and

44 pts FFX>GEM. Since approval of NALIRI in 2016, the sequence

GnP>NALIRI (15%) has become the second most common sequential

treatment. Median age for pts receiving FFX in the 1L was 61-62 years, for

pts receiving GnP in their 1L median age was 70 years. Median PFS2 for

all sequences was 9-11 months, median OS was 12-13 months. Updated

data will be presented.

Conclusion: e choice of treatment sequence for pts with mPC is highly

age-dependent. Patients starting with FFX are younger. However, outcome

data on PFS2 and OS are comparable in all those pts. who are t enough

to receive a 2L treatment following either FFX or GnP as 1L. Upcoming

analyses from the TPK are planned for conrmation of these results with

matched cohorts and integration of data on patient reported outcomes

such as health-related quality of life.

Disclosure Statement: e authors declare that there are conicts of interest.

econnections were submitted to the congress organiser KUKM GmbH and

KUKM can disclose them if needed.

293

Regulation of Macrophage-Recruitment in a Pancreatic

Cancer Model - Comparison of the Kampo-Medicine

Juzen-taiho-to with Gemcitabine

Paulina Siebel1; Joanna Napp1,2; Volker Ellenrieder1; Silke Cameron1

1Department of Gastroenterology, Gastrointestinal Oncology and

Endocrinology, University Medical Center Göttingen (UMG)

2Max-Planck Institute of Experimental Medicine, Göttingen

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor

prognosis. A better understanding of molecular mechanisms opens new

therapeutic methods. Japanese traditional herbal medicine (Kampo-

medicine) is immune-modulatory, improves general fatigue and side-

eects of chemotherapy.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 81

Methods: An orthotopic transplantation model of KPC cells into the

pancreas of C57BL/6 mice was established. Mice were treated with

Gemcitabine (Gem, n=12), Juzen-taiho-to (Juz, a standardized Japanese

herbal medicine, n=17), the combination (Gem+Juz, n=17), or NaCl (ctrl,

n=12). Aer sacrice, IHC (CD68, CD45) was performed for macrophage

(MΦ)/ lymphocyte inltration. Immune-modulation, chemokine release

of tumor cells (KPC) and cytokine expression of MΦ (MH-S) were stud-

ied by Western Blot, Realtime PCR and Cytokine Chemokine Array.

Result: Combination treatment prolonged survival. An increase of CD68+

MΦ was observed in Gem+Juz, compared to ctrl (p<0.001). No elevation

was seen for CD206+ M2-MΦ. e number of tumor-associated CD45+

cells did not change. With Juz or Gem+Juz treatment, KPC-cells released

more MΦ-chemoattractant cytokines (i.e. CCL2, CCL20, CXCL2) com-

pared to ctrl or Gem. Juz or Gem+Juz treated MΦ secreted more M1 cyto-

kines (i.e. IL6, TNFa, CXCL10) than ctrl or Gem alone.

Discussion: PDAC cells recruit and polarize MΦ into tumor associated

MΦ (TAM). It is known that TAMs release deoxycytidine (dC), a pyrim-

idine analog, involved in DNA synthesis. Gem is a modied pyrimidine

analog and thus prevents DNA synthesis. Both are taken up by tumor

cells. Based on their molecular similarity, dC competes with Gem for

DNA synthesis/breakdown and thus reduces the therapeutic ecacy

of Gem. We propose that whilst Juz increases M1-MΦ, Gem has more

anti-tumor ecacy.

Conclusion: PDAC-mice live longer with combination therapy. We sug-

gest that this is due to an enhanced cytotoxicity through an increased

number of M1- MΦ enhancing Gem ecacy. To understand the molecu-

lar mechanisms and anti-tumorigenic eect of Juz / chemotherapy treat-

ment, further research is necessary.

Disclosure Statement: e authors declare no conict of interest.

335

Global Expanded Access Program (EAP) to pemigatinib

for patients (pts) with previously treated locally advanced

or metastatic cholangiocarcinoma (CCA) and FGFR2 fusions

or rearrangements

Anouk Lindley1; Gerald Prager2; Michael Bitzer3; Timothy C. Burn1;

Christine F. Lihou1; Elisabeth Croft Richards1

1Incyte Corporation, Wilmington, USA

2Medical University of Vienna, Vienna, Österreich

3Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland

Background: e global pemigatinib (PEMI; INCB054828) EAP was

conducted to make PEMI available to individual pts who, in the opin-

ion and clinical judgment of the treating physician, would benet from

receiving PEMI for the treatment of locally advanced or metastatic CCA

and cannot be treated satisfactorily with an authorized medicinal product.

Methods: Eligible pts were aged ≥18 years with previously treated CCA

and FGFR2 fusions/rearrangements, and with documented disease pro-

gression/intolerance aer ≥1 line of prior systemic therapy. Pts received

oral PEMI 13.5 mg QD until dose reduction, discontinuation or EAP

completion following local approval and access. Data collected were

demographics, duration of therapy, dosing and discontinuations, FGFR2

testing/status, and safety. Various testing platforms were allowed for

assessment of FGFR2 status.

Result: A total of 79 pts received PEMI from 68 physicians through the

EAP from January 2020 to June 2021 (Europe, 86.1%; Canada, 8.9%; USA,

3.8%; Israel, 1.3%; median age, 61 years [IQR, 48–67]; women, 67.1%;

≥1 reported prior therapy, 89.9%, most commonly cisplatin-gemcitabine

[41.8%] and FOLFIRI [8.9%]). Median duration of treatment was 102 days

(IQR, 45–189), with several pts remaining on PEMI at data cut o. Of the

79 pts receiving PEMI 13.5 mg QD, 11 (13.9%) reduced dose (9 mg QD,

n=8; 4.5 mg QD, n=1; unspecied, n=2) due to AEs; 9 (11.4%) pts discon-

tinued due to AEs. Pts were most commonly tested for FGFR alterations

using local assay (38.0%), FoundationOneTM (36.7%), or ermoFisher

OncomineTM (17.7%) platforms. Among all 79 treated pts, 50 (63.3%)

experienced all cause AEs, most commonly hyperphosphatemia (25.3%);

23 (29.1%) experienced serious AEs, most commonly disease progression

(3.8%), death (3.8%), or hypercalcemia (2.5%).

Discussion: In a real-world setting, PEMI safety was consistent with its

known AE prole in previously treated pts with CCA and FGFR2 fusions/

rearrangements.

Conclusion: e results indicate that pts with CCA should receive molec-

ular testing to identify eligible pts who might benet from PEMI.

Disclosure Statement: e authors declare the following: Gerald Prager served as

a consultant and on symposiums for Merck Serono, BMS, Roche, Amgen, Sano,

Lilly, Servier, Taiho, Bayer, Halozyme, MSD, Celgene, Incyte, and Terumo; Michael

Bitzer served as a consultant and on symposiums for Roche Pharma, Incyte,

MSD, BMS, and Bayer; Anouk Lindley, Timothy C. Burn, Christine F. Lihou, and

Elisabeth Cro Richards each hold Incyte stock and were employees at Incyte at

time work was done.

344

Identication of a prognostic systemic inammation

score (SIS) in patients (pts) with advanced intrahepatic

cholangiocarcinoma (iCCA) treated with palliative

chemotherapy (CTX)

Marlene Maßmann1; Andreas Paul2; Peter Markus3; Brigitte Schumacher4;

David Albers4; Saskia Ting5; Bastian Mende6; Julius Röhrle1;

Isabel Virchow1; Vivian Katrin Rosery1; Katharina Laue1; Gregor Zaun1;

Karina Kostbade1; Michael Pogorzelski1; Kurt Werner Schmid5;

Jens Siveke1; Hans-Ulrich Schildhaus5; Martin Schuler1; Marcel Wiesweg1;

Stefan Kasper-Virchow1

1Universitätsklinikum Essen, Westdeutsches Tumorzentrum , Innere Klinik

(Tumorforschung), Essen, Deutschland

2Universitätsklinikum Essen, Klinik für Allgemein-, Viszeral- und

Transplantationschirurgie, Essen, Deutschland

3Elisabeth-Krankenhaus Essen, Klinik für Allgemein-, Viszeral- und

Unfallchirurgie, Essen, Deutschland

4Elisabeth-Krankenhaus Essen, Klinik für Innere Medizin und Gastroenterologie,

Essen, Deutschland

5Universitätsklinikum Essen, Institut für Pathologie, Essen, Deutschland

6Universitätsklinikum Essen, Zentral Apotheke, Essen, Deutschland

Background: Systemic inammatory response parameters (SIR) are

known prognostic markers in dierent tumour entities but have not been

evaluated in pts with iCCA.

Methods: SIR markers were retrospectively evaluated in 219 pts with

iCCA treated with systemic CTX at the West German Cancer Center

Essen. e SIR markers: neutrophile/lymphocyte ratio (NLR), lympho-

cyte/monocyte ratio (LMR), CRP and the modied Glasgow Prognostic

Score (mGPS) were correlated with clinico-pathological ndings,

response to CTX (ORR), progression-free (PFS) and overall survival (OS)

using Kaplan-Meier curves, univariate and multivariate Cox proportional

models.

Results: Median overall survival (OS) of the study population was 17.3

months (95% CI 12.9-24.8). In total, 138 (63%) pts received palliative

CTX only, while 81 (37%) pts were resected in curative intent. Median

disease-free survival (DFS) in the latter pts was 12.3 months (95% CI 9.7-

23.1), with a median OS of 39.2 months (95% CI 36.0-48.4). e median

OS from start of palliative CTX (OSpall) was 10 months (95% 8.6-12.4).

Based on the evaluated SIR markers, we created a combined Systemic

Inammatory Score (SIS), which signicantly correlated with ORR, PFS

and OSpall. Pts with high SIS (≥2) had a signicantly reduced OSpall com-

pared to pts with SIS 0 (HR for SIS 2: 6.82, 95% CI 2.32-20.07, p<0,001 and

HR for SIS 3: 15.9, 95% CI 4.99-50.66; p<0,001). In multivariate analysis

for OSpall and PFS including known prognostic markers, only the Eastern

Oncology Cooperative Group performance score (ECOG) and the SIS

were independent prognostic factors (ECOG HR 1.91, 95% CI 1.15-3.15,

p<0.012; SIS HR 3.16 95% CI 1.79-5.57, p<0.001).

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts82

Conclusions: We identied a new, easily applicable SIS based on routinely

assessed serum markers as independent prognostic risk score, which has

potential to support therapeutic decision-making in pts with advanced

iCCA treated with systemic CTX.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

355

Comparison of esophagectomy and gastrectomy in patients

with adenocarcinoma of the esophagogastric junction (AEG)

type II – a retrospective cohort study on overall, recurrence

free survival and recurrence rates

Roman Stürzl1; Michael Gerken2,3; Monika Klinkhammer-Schalke2,3;

Armin Pauer2,3; Pompiliu Piso4

1University of Regensburg, Faculty of Medicine, Regensburg, Deutschland

2Tumor Center , Institute for Quality Management and Health Services Research,

University of Regensburg, Regensburg, Deutschland

3Bavarian Cancer Registry, Regional Centre Regensburg, Bavarian Health and

Food Safety Authority, Regensburg, Deutschland

4Hospital Barmherzige Brüder Regensburg, Clinic for General and Visceral

Surgery, Regensburg, Deutschland

Background: e incidence of adenocarcinoma of the esophagogastric

junction (AEG) has signicantly increased. However, the best surgical

therapy for cardiac cancer AEG type II is still subject of current research.

e goal of this retrospective cohort study is to compare survival and

recurrence rates in patients, who underwent either thoracoabdominal

esophagectomy (TAE) or transhiatal extended gastrectomy (TEG).

Methods: e study is based on a cohort of 323 patients diagnosed with

AEG type II between 2002 and 2020, recorded by the population-based

clinical cancer registry of Tumor Center Regensburg. Of the included

patients 63 underwent TAE and 209 TEG. In order to compare overall sur-

vival, recurrence rates, and recurrence free survival, we applied Kaplan-

Meier-method, uni- and multivariable Cox-regression and in addition 1:3

propensity score matching (PSM, n=185), to avoid confounding bias.

Result: Our analysis showed no statistically signicant dierence con-

cerning overall survival, with a trend towards higher survival rates aer

TAE (p=0,333). In contrast a trend towards higher cumulative recurrence

rates, especially for distant metastases, was found aer TAE (p=0,201),

which was signicant aer PSM (p=0,049). is trend was not observed

for the time aer 2016 (p=0,993), in which over 50% of TAE were per-

formed. No dierences were found regarding recurrence-free survival

(p=0,772).

Discussion: Our ndings in a rather small cohort are concordant to

most studies showing a trend towards better survival aer TAE. Another

German study found no signicant dierence regarding recurrence free

survival as well.

Conclusion: Both approaches seem reasonable in treatment of AEG type

II. A non-signicant trend towards TAE concerning overall survival could

be demonstrated. TEG showed a slight benet concerning recurrence

rates.

Disclosure Statement: e authors declare no conict of interest.

357

Ramucirumab beyond progression plus TAS 102 in patients

with advanced or metastatic adenocarcinoma of the stomach

or the gastroesophageal junction, after treatment failure on

a ramucirumab based therapy - nal results of the phase II

RE-ExPEL study

Thorsten O. Goetze1; Alexander Stein2; Sylvie Lorenzen3; Eray Gökkurt2;

Timursah Habibzade4; Peter Herhaus3; Disorn Sookthai1; Claudia Pauligk1;

Kristina Ihrig1; Salah-Eddin Al-Batran1

1Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest,

Frankfurt am Main

2Hämatologisch-Onkologische Praxis Eppendorf (HOPE) , Facharztzentrum

Eppendorf, Hamburg

3München Klinikum rechts der Isar der TU München , II. /III. Medizinische Klinik

und Poliklinik, München

4Krankenhaus Nordwest, University Cancer Center Frankfurt

Background: Based on results of prior trials, it seems promising to

combine Ramucirumab (Ram) beyond progression (PD) with TAS-102

(triuridine/tipiracil). e purpose of RE-ExPEL is to investigate the tol-

erability, safety and benet of Ram beyond PD in combination with TAS-

102 in advanced esophagogastric adenocarcinoma (EGA).

Methods: is is a multicenter, non-randomized, open-label investigator

initiated pilot trial. 20 Ram-pretreated patients (pts) with advanced EGA

were enrolled to a maximum of 4 cycles of ram 8mg/kg every 2 weeks

(days 1, 15 qd28) plus TAS-102 35 mg/m2/p.o. bid (d1-5 and d8-12 qd28).

Primary endpoint (EP) is tolerability and toxicity, dening a positive trial

if SAE rate according (acc.) to CTCAE 5.0 will increase less than 30% (up

to 55%) compared with results from TAGS (SAE-rate 43%) . Secondary

EPs are further safety and ecacy data. Safety evaluation was conducted

when the last patient received two cycles or prematurely discontinued

(EOT for any reason).

Result: 20 pts were enrolled between Oct 2020 and Aug 2021, 20% gas-

tric and 80% GEJ- cancers, 55% of pts with ECOG 0. Results of the nal

analysis showed that only 25% of pts had at least one SAE and the total no.

of SAEs was only 8, all without relation to systemic therapy, no SUSAR

reported. No SAE showed fatal outcome. RE-ExPEL was able to show a

median OS of 8.44 mo and a DCR of 60%.

Discussion: e safety data showed a favorable safety prole with less tox-

icity for Ram+TAS-102, maybe due to the long disease stabilization and

therefore less tumor associated symptoms. Regarding the primary safety

EP, the trial was positive with even a decrease in SAE rate compared with

TAGS.

Conclusion: Ram + TAS-102 in pts with advanced EGA beyond PD

showed a favorable safety prole. Furthermore, RE-ExPEL was able to

show very promising ecacy data for the combination Ram+TAS-102

with median OS of 8.44 mo. Ram+TAS-102 seems to be more eective

than TAS-102 alone acc. to TAGS-trial respecting the limitation of the one

arm study design with only 20pts. e combination needs further evalua-

tion in a randomized phase III trial.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 83

399

Characterization of Pontin, Reptin and CD82 in Esophageal

Adencocarcinoma

Alexandra Ludwig; Beate Limberger; Orestis Lyros; Ines Gockel;

René Thieme

Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,

Thorax- und Gefäßchirurgie, Leipzig, Deutschland

Background: e incidence of esophageal adencocarcinoma (EAC)

has increased in the Western world. Regardless to improved periopera-

tive chemotherapies and surgical approaches, the prognosis for EAC in

advanced stages is poor. Pontin (RUVBL1) and Reptin (RUVBL2) are

associated with the chromatin remodeling complexes, transcription reg-

ulation, DNA damage response and the Wnt/ß-Catenin pathway. eir

overexpression has been reported in several cancer entities. CD82 (KAI1)

is a tumor suppressor gene, and its lack is related to metastasis formation

and cancer progression. Transcriptional activity of CD82 might be regu-

lated by Pontin and Reptin.

Methods: An in vitro cell model for the Barrett’s esophagus (squamous

epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B) and

esophageal adenocarcinoma (OE33, OE19, SK-GT-4, FLO-1)) has been

used. Pontin mRNA expression was analyzed in 5-FU treated OE33 and

OE19 cells for 24h by q-RT-PCR and western blot analyses. Antisense

LNA Oligonucleotides (GapmeRs, Qiagen) were used to achieve a tran-

sient knockdown of CD82 in OE33 and OE19.

Result: Pontin and Reptin were expressed in all investigated cell lines

and both showed a signicant overexpression in CP-B, OE19 and FLO-1

cells on mRNA level. Expression of CD82 was shown to be present in all

cell lines, except in the metaplastic cell line CP-A. A signicantly lower

expression was observed in CP-A, OE33 and SK-GT-4 cells. e Pontin

mRNA expression was increased aer 5-FU exposure in OE33 and FLO-

1, whereas SK-GT-4 showed a decrease. CD82 was downregulated by

36-62% in OE33 and by 38-52% in OE19.

Discussion: Increased expression levels of Pontin and Reptin and their

contribution to the Wnt/ß-Catenin pathway activation could be a novel

biomarker in the progression of EAC. Low expression levels of CD82

might inuence the metastatic ability of EAC cells.

Conclusion: Further molecular characterizations are needed to elucidate

their impact on cell proliferation, cellular motility, Wnt-pathway activa-

tion, and their role in the carcinogenesis of EAC.

Disclosure Statement: e authors declare no conict of interest.

425

Atezolizumab plus Bevacizumab in second or further line

therapy in patients with advanced stage hepatocellular

carcinoma (HCC): data on ecacy and safety from a

multicenter real-life cohort

Friedrich Sinner1; Matthias Pinter2,3; Bernhard Scheiner2,3;

Thomas J. Ettrich4; Niklas Sturm4; Maria Angeles Gonzalez-Carmona5;

Oliver Waidmann6,7; Fabian Finkelmeier6,7,8; Vera Himmelsbach6;

Enrico De Toni9; Najib Ben Khaled9; Raphael Mohr10; Thorben Fruendt11;

Fabian Kütting12; Florian van Boemmel13; Sabine Lieb13; Sebastian Krug14;

Dominik Bettinger15; Michael Schultheiss15; Leonie Jochheim16; Jan Best1,17;

Christian Müller1; Marino Venerito1

1Department of Gastroenterology, Hepatology and Infectious Diseases,

Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Deutschland

2Division of Gastroenterology and Hepatology, Medical University of Vienna,

Department of Internal Medicine III, Vienna, Österreich

3Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna,

Österreich

4Department of Internal Medicine I, Ulm University Hospital, Ulm, Deutschland

5Department of Internal Medicine I, University Hospital of Bonn, Bonn,

Deutschland

6Department of Gastroenterology, Hepatology and Endocrinology, University

Hospital Frankfurt, Frankfurt (Main), Deutschland

7University Cancer Center Frankfurt, University Hospital Frankfurt, Frankfurt

(Main), Deutschland

8Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt (Main),

Deutschland

9Department of Medicine II, University Hospital, LMU Munich, Munich,

Deutschland

10Department of Hepatology & Gastroenterology, Charité University Medicine

Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Deutschland

11Department of Internal Medicine, Gastroenterology & Hepatology, University

Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

12Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University

Hospital Cologne, University of Cologne, Cologne, Deutschland

13Division of Hepatology, Department of Medicine II, Leipzig University Medical

Center, Leipzig, Deutschland

14Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg,

Halle, Deutschland

15Department of Medicine II, Medical Center University of Freiburg, University of

Freiburg, Freiburg, Deutschland

16Department of Gastroenterology and Hepatology, University Hospital Essen,

Essen, Deutschland

17Department of Internal Medicine, University Hospital

Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum,

Deutschland

Background: Atezolizumab plus Bevacizumab (Atezo/Bev) is the stan-

dard of care in rst line systemic therapy for advanced stage hepatocellular

carcinoma (HCC). Data on ecacy and safety of Atezo/Bev in patients

who did not have access to this option as rst line therapy are lacking.

Methods: Patients with HCC who received Atezo/Bev in second or fur-

ther lines between December 2018 and March 2022 were retrospectively

identied across 13 centers in Germany and Austria. Patient characteris-

tics, tumor response rates, progression free survival (PFS), overall survival

(OS) and adverse events (AE) were analyzed.

Result: Overall, 50 patients were identied, 41 (82%) were male. e

median age at the start of Atezo/Bev was 65 years, 41 (82%) patients had

liver cirrhosis, 30 (73%) Child A, 9 (22%) B and 2 (5%) C. e most com-

mon etiologies for the underlying liver disease were nonalcoholic fatty

liver disease (NAFLD) in 14 (28%), alcohol abuse in 13 (26%), hepatitis

C virus (HCV) infection in 11 (22%) and hepatitis B virus (HBV) infec-

tion in 6 (12%) cases, respectively. Overall, 34 patients (68%) received

Atezo/Bev in second line and 16 (32%) in further lines. Best radiologi-

cal tumor responses were complete remission in 1 (2%), partial remis-

sion in 15 (30%), stable disease in 18 (36%) and progressive disease in

9 (18%) patients resulting in a disease control rate of 68% and an objec-

tive response rate of 32%. Median OS was 16.0 months (95% condence

interval 5.6-26.4 months). Median PFS on Atezo/Bev was 7.1 months

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts84

(95% condence interval 4.4-9.8 months). Adverse events (AE) grade 3-4

were observed in 7 (14%) and led to death of 3 patients (6%). ere were

5(10%) bleeding events of grade ≥ 3, one of them (2%) with fatal outcome

was reported.

Discussion: e identication of risk factors for severe complications may

further improve the outcome in patients with advanced HCC receiving

Atezo/Bev.

Conclusion: Atezo/Bev is eective in patients with advanced stage HCC

who did not have access to this option as rst line therapy. e safety pro-

le was consistent with previous reports.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

428

Tertiary lymphoid structures in PDAC resemble lymphoid

follicles in secondary lymphoid organs by organization,

function and gene expression

Jonas Lehmann1; Martin Thelen1; Simon Schran1; Ella Preugszat1;

Kerstin Wennhold1; Maria Garcia-Marquez1; Philipp Lohneis2; Heike Löser2;

Felix Popp3; Michael von Bergwelt-Baildon1,4,5; Christiane J. Bruns3;

Alexander Quaas2; Hans. A. Schlößer1,3

1University of Cologne, Faculty of Medicine and University Hospital Cologne,

Center for Molecular Medicine Cologne, Köln, Deutschland

2University of Cologne, Faculty of Medicine and University Hospital Cologne,

Institute of Pathology, Köln, Deutschland

3University of Cologne, Faculty of Medicine and University Hospital Cologne,

Department of General, Visceral, Cancer and Transplantation Surgery, Köln,

Deutschland

4LMU Munich, LMU clinic, Department of Internal Medicine III, München,

Deutschland

5Deutsches Krebsforschungszentrum, DKTK – Das Deutsche Konsortium für

translationale Krebsforschung, Heidelberg, Deutschland

Background: Tertiary lymphoid structures (TLS) are gaining attention

in the recent years as secondary lymphoid organs (SLO) like structures,

which are involved in induction and enhancement of anti-tumor immune

responses. ese TLS are induced or enhanced in the tumor microenvi-

ronment and are assumed to represent hotspots for T cell priming, B cell

activation and dierentiation, which cause cellular and humoral anti-tu-

mor immune responses

Methods: We performed immunohistochemistry staining of 120 primary

pancreatic ductal adenocarcinoma (PDAC) patients for CD20, CD3, CD8,

FOXP3 and FDCM1 to analyze spatial distribution of tumor-inltrating

lymphocytes. Comparison of structural components of lymphoid follicles

between TLS and SLOs was done by 5-color immunouorescence stain-

ing. Tissue extraction by laser microdissection and Nanostring-base RNA

expression analysis was conducted to compare gene expression in TLS,

PDAC, SLOs and normal pancreatic tissue.

Result: TLS were found in 85 % of all patients, but frequency of TLS dif-

fered between patients. While TLS were mainly localized in a 2000 µm

invasive tumor margin 50 % of all patients showed at least a few intra-

tumoral TLS. Patients with high density of TLS inside and surrounding

the tumor, as well as high T cell inltration showed higher overall sur-

vival. Five-color Immunouorescence revealed similarities in the archi-

tecture of TLS with secondary lymphoid organs. Nanostring analysis of 12

patients conrmed also functional similarities of TLS and SLOs by largely

overlapping expression patterns.

Discussion: As described before our results conrm benecial impact of

TLS abundance in the tumor microenvironment in PDAC. Our study is

the rst comparing the immune functional expression patterns between

SLOs and TLS in PDAC.

Conclusion: Our results indicate the close similarities of TLS and SLOs

in organization, function and gene expression patterns for better under-

standing of the tumor microenvironment in PDAC and improvement of

future therapies.

Disclosure Statement: e authors declare no conict of interest.

443

Ecacy and safety of atezolizumab and bevacizumab in the

real-world treatment of advanced hepatocellular carcinoma:

experience from four tertiary centers

Vera Himmelsbach1; Matthias Pinter2,3; Bernhard Scheiner2,3;

Marino Venerito4; Friedrich Sinner4; Carolin Czauderna5,6;

Jens U. Marquardt5,6; Jörg Trojan1; Oliver Waidmann1,7;

Fabian Finkelmeier1,7,8

1University Hospital Frankfurt, Frankfurt, Department of Gastroenterology,

Hepatology and Endocrinology, Frankfurt am Main, Deutschland

2Medical University of Vienna, Vienna, Austria , Division of Gastroenterology and

Hepatology, Department of Internal Medicine III, Wien, Österreich

3Medizinische Universität Wien, Liver Cancer (HCC) Study Group Vienna , Wien,

Österreich

4Otto-Von Guericke University Hospital, Magdeburg, Germany, Department

of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg,

Deutschland

5University Medical Center, Campus Lübeck, Department of Medicine I, Lübeck,

Deutschland

6Johannes Gutenberg-Universität Mainz, Department of Internal Medicine I,

Mainz, Deutschland

7University Hospital Frankfurt, University cancer center Frankfurt, Frankfurt am

Main, Deutschland

8Goethe University Frankfurt am Main, Frankfurt Cancer Institute , Frankfurt am

Main, Deutschland

Purpose: e present multicenter cohort study aimed at assessing the e-

cacy and safety of atezolizumab and bevacizumab (A+B), the new rst line

therapy for advanced HCC, in a real-life setting.

Methods: We included prospectively collected patients with advanced

HCC receiving rst-line treatment with A+B at four cancer centers

in Germany and Austria between December 2018 and August 2021.

Demographics, overall survival (OS) and adverse events were evaluated

until September 15th, 2021.

Results: In total we included 66 patients. e median age was 66 years

and 54 (82%) were male. Predominantly underlying liver disease was

alcohol-related liver cirrhosis in 24 patients (36%) and NASH/NAFLD in

18 patients (27%). Most patients had compensated cirrhosis (n=34; 52%),

while Child-Pugh class B was observed in 23 patients (35%) and class

C cirrhosis in 5 patients (8%). 27 patients (41%) died during follow-up.

During a median follow-up period of 211 days from A+B treatment initi-

ation, median OS was not reached. e estimated survival rate was 66% at

6 months and 56% at 12 months. Patients with compensated cirrhosis had

an estimated survival rate of 85% at 6 and 78% at 12 months. In 22 patients

(33%), the administration of bevacizumab was paused during the course

of therapy, mostly due to perceived elevated bleeding risk. 14 patients

(21%) developed gastrointestinal bleeding events during A+B treatment.

One patient died in association with gastrointestinal bleeding.

Discussion: e high bleeding incidence highlights the importance of

endoscopic variceal screening before and during A+B therapy.

Conclusions: Based on the good ecacy and safety results derived from

the phase 3 study (IMBRAVE150), A+B is now considered the new stan-

dard of care for advanced, unresectable HCC. Patients in a real-world

clinical practice had more advanced liver disease and therefore showed

lower survival at 6 and 12 months so far.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 85

490

Characterization of Premalignant and Malignant Pancreatic

Cancer Cells in a Physiological and Inamed Hepatic

Microenvironment

Claudia Seemann; Svenja Quaester; Silje Beckinger; Tina Daunke;

Lisa-Marie Philipp; Isaac Musong Mboni Johnston; Susanne Sebens

Institut für Experimentelle Tumorforschung, Christian-Albrechts-Universität zu

Kiel, UKSH, Campus Kiel, Haus U30, Kiel, Deutschland

Background: Most pancreatic ductal adenocarcinomas (PDAC) are diag-

nosed at an advanced stage oen already with distant metastases. e liver

is the main site of metastasis and patients who could undergo surgical

resection of primary PDAC oen develop liver metastases aer or even

during adjuvant therapy. us, this study investigated whether the hepatic

microenvironment (HME) impacts metastasis-associated processes in

premalignant and malignant pancreatic ductal epithelial cells (PDEC).

Methods: To analyze the impact of the HME on PDEC, premalignant

H6c7-Kras (Kras) and malignant PancTu1 PDEC were indirectly cocul-

tured with hepatic stellate cells (HSC), representing a physiological HME

or hepatic myobroblasts (HMF), simulating an inamed HME. Aer

5 days, proliferation was measured via vital cell count and Ki-67 uo-

rescence activated cell scanning (FACS). PDEC were also characterized

regarding an Epithelial-Mesenchymal-Transition (EMT) phenotype and

cancer stem cell (CSC) properties using colony formation assay (CFA) and

single and combined FACS staining.

Result: We demonstrated an increased cell growth of PDEC aer cocul-

ture with HMF compared to HSC. Aer HSC coculture, Kras cells formed

a signicantly higher number of colonies compared to HMF coculture,

which was observed by trend also in PancTu1 cells. Ki-67 FACS stain-

ing revealed two PDEC populations which were similar in all cocoltures:

Ki-67 high (90%) and low (10%). Ki-67 high proliferating PDEC were

characterized by a CSC and mesenchymal phenotype, an eect which was

more pronounced in PancTu1 than in Kras cells.

Discussion: ese data indicate that HME in dependence on the inam-

matory status is an important determinant for cell growth along with

EMT and CSC properties in premalignant and malignant PDEC.

Conclusion: Overall, these ndings support the view that a physiological

HME is able to control PDEC growth and contribute to maintenance of

CSC properties while an inamed HME strongly promotes proliferative

activity of PDEC.

Disclosure Statement: e authors declare no conict of interest.

492

Implementation and benet of the S3 guideline in resected

pancreatic cancer: results of a population-based multicenter

registry study in East Bavaria

Julia Gumpp1; Alina Kupper1,2; Michael Gerken2,3; Armin Pauer2,3;

Monika Klinkhammer-Schalke2,3; Bettina M. Rau1

1Abteilung für Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Neumarkt,

Neumarkt in der Oberpfalz, Deutschland

2Tumorzentrum Regensburg - Institut für Qualitätssicherung und

Versorgungsforschung, Universität Regensburg, Regensburg, Deutschland

3Regionalzentrum Regensburg, Bayerisches Krebsregister, Bayerisches

Landesamt für Gesundheit und Lebensmittelsicherheit, Regensburg,

Deutschland

Background: In 2007, the rst German S3-guideline for exocrine pan-

creatic cancer was published. In a retrospective cohort study we investi-

gated the degree of implementation and possible eects of the guideline

recommendations in patients with resectable pancreatic cancer in clinical

routine practice.

Methods: Based on the data from the clinical cancer registry at the

Regensburg Tumor Center, two patient groups with resectable pancreatic

ductal adeocarcinoma in stages UICC I-III were analyzed. Group 1: treat-

ment period 2000-2007 (n = 88) and group 2: treatment period 2008-2017

(n = 307) were compared with regard to patient and tumor characteristics,

surgical technique, adjuvant/additive chemotherapy and overall survival.

Result: In group 2, patients’ age, (p < 0.001), comorbidities (p = 0.002),

and lower tumor stages (p = 0.022) were signicantly higher/more fre-

quent than in group 1. e percentage of patients undergoing preoperative

tumor board discussion rose from 9.3% to 43.4% (p < 0.001). Postoperative

tumorboard discussions rose from 32.6% to 87.7% (p < 0.001). e mean

number of dissected and examined lymph nodes increased from 14.5

to 19.2 (p < 0.001), whereas the percentage of R1-resections remaind

unchanged. In group 2, 67.1% of the patients received adjuvant/addi-

tive chemotherapy compared to only 38.6% in group 1 (p < 0.001). e

median overall survival was 26.9 in group 2 and 19.5 months in group 1

(HR 0.805; 95 % CI 0.622-1.041; p = 0.098). Aer adjusting for risk fac-

tors, group 2 showed a signicantly better survival compared to group 1

with an HR of 0.736 (95% CI 0.559-0.971; p = 0.030).

Discussion: e limitations of a retrospective cohort-study were ade-

quately addressed by risk-adjustment with multivariable regression

analyses.

Conclusion: Our results show a good implementation and acceptance of

the S3-guideline recommendations in resected exocrine pancreatic can-

cer in clinical practice. A signicant rise of interdiciplinary tumor board

discussion and adjuvant/additive chemotherapy aer resection seems to

contribute to an increase of overall survival.

Disclosure Statement: e authors declare no conict of interest.

529

Patient blood Management in thoracoabdominal

esophagectomy

Thorsten Perl1; Ina Maria Eberhardt2; Silvia Flachs-Nóbrega1;

Michael B Ghadimi1

1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und

Kinderchirurgie, Göttingen, Deutschland

2Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Göttingen,

Deutschland

Background: Patient blood management (PBM), is a systemic quality

improvement measure to reduce anemia and need of transfusion. For

patients with a preoperative anemia and planned surgery and a transfu-

sion probability of > 10% preoperative steps for hemoglobin (Hb) opti-

mization are recommended. We describe the incidence of preoperative

anemia and transfusion requirement in patients scheduled for thorac-

ic-abdominal esophagectomy in esophageal cancer.

Methods: In a retrospective 1-year chart-analysis, we investigated patients

scheduled for thoracic-abdominal esophagectomy. Preoperative hemo-

globin (Hb), intra- and postoperative transfusion and length of stay

were assessed. Descriptive analysis with values in number (%) and mean

(+/-SD).

Result: 47 patients with thoracic-abdominal esophagectomy have been

included (all year 2019), aged 65.4 (+/- 8) years. 2 patients (4.3%) with

intraoperative (intraOP) transfusion, 7 patients (14.9%) postoperative

(postop) transfusion. All patients were discharged from ICU aer 88.9

(+/- 82.1) h. 13 patients (27.5%) with a preOP Hb of > 13 g/dl received no

transfusion intraOP, 2 (15.4%) a transfusion on ICU. 20 patients (42.6%)

were slightly anemic (preOP Hb ≤ 13 g/dl and > 11 g/dl) and required no

transfusion intraOP, 2 (10%) transfusion on ICU. 14 patients (29.8%) were

distinct anemic (preoperative Hb ≤ 11 g/dl), 1 required transfusion during

surgery, 3 (21.4%) postOP transfusion.

Discussion: We observed with 72.4% a high incidence of preOP anemia

in patients scheduled for thoracoabdominal esophagectomy. e intraOP

transfusion requirement was with 4.3% low, not indicating further PBM

procedures. e high incidence of anemia is due to preoperative onco-

logic treatment, malnutrition, and cancer-associated blood loss plausible.

For further elucidation and preoperative treatment, further diagnostics

are necessary.

Conclusion: e high incidence of preoperative anemia is not direct con-

catenated with transfusion requirement in investigated patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts86

624

Cancer Cachexia in pancreatic adenocarcinoma, prognostic

and predictive parameters in a predened longitudinal

observation

Johanna Meyer-Knees1; Janina Falkenthal2; Christopher Neumann1;

Annika Kurreck1; Annabel Alig1; Thomas Malinka3; Johann Pratschke3;

Hanno Riess1; Sebastian Stintzing1; Uwe Pelzer1

1Department of Internal Medicine, Division of Hematology, Oncology and

Tumorimmunology, Charité Campus Mitte, Charité - Universitätsmedizin Berlin,

Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin,

and Berlin Institute of Health, Berlin, Deutschland

2konZ·E·B·T care GmbH Zentrum für Ernährung, Beatmung und Therapie, Berlin,

3Department of Surgery, Charité Campus Mitte & Campus Virchow Klinikum,

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität

Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin,

Deutschland

Purpose: Cachexia is frequently observed in pancreatic ductal adeno-

carcinoma (PDAC) and is responsible for impaired prognosis. Aim of

this project was to nd predictive and prognostic parameters to identify

patients (pts) at high risk for severe forms of cachexia induced impaired

survival. We focused on systemic inammatory biomarkers.

Methods: 182 pts with PDAC (n=120) and other GI malignancies (n=62,

control) were included in a prospective database and were retrospectively

evaluated according to predetermined parameters (IL-6, CRP, hemoglo-

bin, albumin, CA19-9, the body mass index, bioelectrical assessments).

We used Kaplan-Meier calculations, log-rank tests, Cox survival mod-

els, univariate, and multivariate regression to determine signicant

correlations.

Results: Pts with elevated inammatory marker serum levels had

impaired survival (OS). Pts with CRP levels above 5 mg/L had a median

OS of 12.95 [95% CI: 10.39 – 15.51] months, pts with CRP below ≤5mg/L

had a median OS of 21.08 [95% CI:18.07 – 24.09] months (p = <.001). Pts

with IL-6 levels above >4 pg/ml had a median OS of 15.90 [95% CI 14.48–

17.33] months, pts with IL-6 levels below ≤4 pg/ml had a median OS of

21.08 [95% CI 19.00 – 23.17] months (p = .054). In the multivariate Cox

proportional hazard model both, CRP (HR 1.011, 95% CI 1.003 – 1.020,

p= .010) and IL-6 (HR 1.019, 95%CI 1.000 – 1.038, p = .046), were shown

to be independent prognostic factors for survival. e change in serum

levels of IL-6, but not of CRP, over the course of disease had a signicant

impact on survival. In the control group with other GI malignancies, none

of the inammatory serum marker had a prognostic value.

Conclusions: For pts with PDAC, inammatory markers are prognos-

tic factors for impaired survival, presumably due to the presence of the

accompanying cancer-induced cachexia that is specic to PDAC pts. IL-6

and CRP are sucient surrogate markers to detect risk pts. Our ndings

underlines the importance of further research, investigating these mark-

ers’ as target for therapeutic decisions and interventions.

Disclosure Statement: e authors declare no conict of interest.

643

Functional characterization of Cytoskeleton-Associated

Protein 4 (CKAP4) in esophageal adenocarcinoma cells

Beate Limberger1; Alexandra Ludwig1; Ines Gockel1; Orestis Lyros1;

Renè Thieme1

1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,

Transplantations-, Thorax- und Gefäßchirurgie

Background: Barrett’s esophagus (BE) predisposes to the development of

esophageal adenocarcinoma (EAC). While the incidence of EAC is rap-

idly increasing, its prognosis remains poor. Consequently, the discovery

of new molecular targets for an ecient characterization of EAC patients

is necessary. CKAP4 has been attributed to be increased in various cancer

entities and has a role in tumorigenesis. However, its role in EAC is widely

unknown.

Methods: In an in vitro cell culture model of BE and EAC, CKAP4

expression levels were veried with qPCR and western blot. In OE33

and OE19 cells CKAP4-expression was reduced by transfecting the cells

with CKAP4-siRNA for 48h and 72h. In siCKAP4 transfected cells FACS

(apoptosis), western blot analysis, colony forming assays and spheroid

formation were performed. Using western blot, the impact of CKAP4-

knockdown on the phosphorylation of Akt, MAP-Kinase, GSK3ß and

ß-Catenin was investigated. Furthermore, Ki67- and p21-mRNA-expres-

sion was analyzed in siCKAP4 cells.

Result: CKAP4 was present in all cell lines of the Barrett’s sequence (squa-

mous epithelium, metaplasia, dysplasia and EAC). CKAP4 expression was

lower in OE19 cells than in OE33 cells. Western blot and qPCR analysis

conrmed an ecient siRNA-related knockdown of CKAP4 in EAC cells

aer transfection for 48h and 72h. e phosphorylation of Akt and MAP-

Kinase was decreased in OE33 cells only, suggesting a role of CKAP4

in tumor-associated proliferation, which was conrmed by a decreased

number of colonies in a colony forming assay and smaller spheroids in

siCKAP4 cells.

Discussion: e role of CKAP4 is barely investigated in EAC at this time.

Based on our current results, it can be assumed, that CKAP4 is important

for EAC cell growth and proliferation.

Conclusion: CKAP4 is a Dickkopf-1 (DKK1) receptor and the DKK1-

CKAP4-axis might promote cell proliferation independently to the Wnt-

pathway. A further CKAP4 characterization is necessary, particularly

focusing on the CKAP4-DKK1-axis to provide more evidence for its con-

tribution in EAC development.

Disclosure Statement: e authors declare no conict of interest.

678

Meeting Medical Need - Development of a High-Throughput

Assay Using Pancreatic Cancer Patient Derived Organoids as a

Tool for Personalized Medicine

Sushmitha Sankarasubramanian1,2; Maya Niethard3,4; Christian Pilarsky2;

Christian Regenbrecht1,5,6; Lena Wedeken1

1CELLphenomics GmbH, Berlin, Deutschland

2Chirurgische Klinik, Universitätsklinikum Erlangen, Department of Surgery,

Erlangen, Deutschland

3Helios Klinikum Berlin-Buch, Department of Tumor Orthopedics, Berlin,

Deutschland

4Universitätsmedizin Greifswald, Klinik und Poliklinik für Orthopädie und

Orthopädische Chirurgie, Greifswald, Deutschland

5ASC Oncology GmbH, Berlin, Deutschland

6Universitätsklinikum Göttingen, Institute for Pathology, Göttingen,

Deutschland

Background: Pancreatic cancer is a highly heterogeneous, clinically

challenging, and oen therapy-resistant disease that is almost impos-

sible to target with a “one drug ts all” approach and therefore the

future treatment should move towards personalized medicine. Reverse

Clinical Engineering, a combined targeted phenotypic approach utilizing

patient-derived organoids allows the identication of eective treatment

in a personalized manner.

Methods: Patient tumor-derived organoids are used to perform func-

tional drug screening and the individual responses for each tumor are

identied. We developed and optimized assay conditions to use pancreatic

cancer patient-derived organoids to perform routine drug screening in a

potential high throughput manner.

Result: With this platform, we can analyze the individual tumor response

to standard of care chemotherapeutics but also novel therapeutic reg-

imen and establish a drug sensitivity prole for each individual tumor.

Using this approach, we were able to identify dierences in therapeutic

responses between dierent patient models.

Discussion: Our approach using patient-derived organoid models of

pancreatic cancer allows to identify eective treatment approaches in a

potentially personalized manner. Integrating genomic and transcrip-

tomic sequencing data to the responders and non-responders identied

in the assay will further pave the way to uncover the drug sensitive and

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 87

resistance mechanisms, potentially leading to the identication of predic-

tive biomarkers.

Conclusion: High-throughput drug screening using patient-derived

organoids possess a real opportunity to pave the way to real personalized

medicine in pancreatic cancer.

Disclosure Statement: e authors declare the following: CRAR and Christian

Regenbrecht is shareholder at CELLphenomics GmbH, a company oering drug

screens on organoid models, and ASC Oncology GmbH, a company involved in

patient specic therapy prediction.

685

Bioinformatics Analysis of the Expression and Prognosis for

BGN, COL1A1, SPARC, TIMP1 in Gastric Cancer

Chuang Yang1; René Thieme1

1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,

Transplantations-, Thorax- und Gefäβchirurgie

Background: e incidence of gastric cancer (GC) has increased world-

wide. e clinical early symptoms of GC are not obvious, and most

patients have advanced tumor stages at diagnosis. We used bioinformatics

screening tools, to assess gastric cancer biomarkers and their prognos-

tic values through the identication of key dierentially expressed genes

(DEGs).

Methods: Data sets from GC patients (GSE54129, GSE79973, and

GSE118916, GEO DataSets) were downloaded. e overlapped DEGs

and constructed protein-protein interaction (PPI) networks were identi-

ed. Aerwards, the module and hub gens were conducted by Cytoscape

soware and the relationship between hub genes and clinical information

in dierent databases including Oncomine, Gene Expression Proling

Interactive Analysis (GEPIA), e Human Protein Atlas (THPA), Kaplan-

Meier Plotter and TIMER were investigated.

Result: Top 10 hub genes were selected including FN1, IL6, COL1A1,

COL1A2, BGN, CXCL8(IL8), TIMP1, THBS2, SPARC, THBS1. e

expression levels of BGN, COL1A1, COL1A2, CXCL8, FN1, SPARC,

THBS2, TIMP1 were higher in gastric cancer tissues than in normal gas-

tric tissues. BGN, COL1A1, COL1A2, SPARC, THBS1, THBS2, TIMP1

were related to the tumor classication. BGN, FN1, SPARC, COL1A1,

TIMP1 were easier detected in tumor samples compared with normal tis-

sues. Survival analysis showed that the high expression of BGN, COL1A1,

COL1A2, FN1, SPARC, THBS2, TIMP1 were related to lower overall sur-

vival. BGN, COL1A1, SPARC, TIMP1 were signicantly associated with

the level of macrophage inltration.

Discussion: BGN, COL1A1, SPARC, TIMP1 had a higher expression in

gastric cancers than in healthy gastric mucosa and they were more related

to clinical parameters. ey may promote the development of GC by reg-

ulating the PI3K/Akt signaling pathway during the progression of GC.

Conclusion: Further researches should be conrmed in in vitro and in

vivo experiments to elucidate their impact on cell proliferation, cellular

motility, PI3K/Akt-pathway activation, and their role in the carcinogen-

esis of GC.

Disclosure Statement: e authors declare no conict of interest.

697

Immunomodulatory capacity of histone deacetylase

inhibition in esophageal adenocarcinoma due increased

HLA-ABC expression

Robert Nowotny1; Claudia Marti Grifol1; Orestis Lyros1; Ines Gockel1;

René Thieme1

1Univesitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,

Thorax- und Gefäßchirurgie

Background: HLA class I expression in highly important, as it is needed

for the presentation of tumor-associated neo-antigens. Histone deacetyl-

ase (HDAC) are responsible for epigenetic modications even in cancer

cells. Whether, the inhibition of HDACs has an Immunomodulatory

eect in cancer cells is widely unknown, especially, in esophageal adeno-

carcinoma cells (EAC).

Methods: e EAC cells OE33 and OE19 and PBMCs were treated by

six HDACi (vorinostat, DKK137, entinostat, TMP269, PCI34051 and

tubostatin A) with 300nM and 600nM for 48h. e IC50 and HLA-ABC

expression by FACS analyses were determined aer HDACi treatment.

Results: DKK137, an experimental HDACi had a sub-micromolar IC50

in OE33 (0.44µM) and OE19 (0.60µM) cells. Whereas vorinostat and

entinostat revealed IC50 values between 1-4.5µM. TMP269, PCI34051

and tubostatin A showed IC50 values > 20µM. Obviously, the HLA-ABC

expression is diverse in EAC cancer cells, as OE33 showed a 7fold higher

HLA-ABC expression than OE19 cells. Both, OE33 and OE19 cells showed

increased HLA-ABC expression when they were treated by DKK137 and

entinostat. PBMCs did not show an increase in HLA-ABC expression by

the used HDACi.

Discussion: We were able to investigate six HDACi for their anti-prolif-

erative capacity in EAC cells and their impact to the HLA-ABC surface

expression.

Conclusion: e impact of an HDACi treatment to the tumor immunol-

ogy due to a HLA-mediated increased neo-antigen presentation might be

a novel treatment concept for HDACi in EAC patients.

Disclosure Statement: e authors declare no conict of interest.

714

HEPANOVA: Final ecacy and safety results from a phase

2 study of Tumor Treating Fields (TTFields, 150 kHz)

concomitant with sorafenib in advanced hepatocellular

carcinoma (HCC)

Eleni Gkika1; Yann Touchefeu2; Teresa Macarulla Mercade3;

Antonio Cubillo Gracián4; Robert Thimme1; Thomas Brunner5;

Monika Pazgan-Simon6; Thomas Seuerlein7; Anca-L. Grosu1

1Medical Centre, University of Freiburg, Freiburg, Germany

2Hépato gastro entérologie et oncologie digestive, IMAD CHU Nantes, France

3Vall d’Hebrón University Hospital and Vall d’Hebrón Institute of Oncology,

Barcelona, Spai

4Centro Integral Oncológico Clara Campal HM CIOCC, Hospital Universitario HM

Sanchinarro, Madrid, Spain

5Medical Centre, University of Magdeburg, Magdeburg, Germany

6Department of Infectious Diseases and Hepatology, Wroclaw Medical

University, Wroclaw Medical University, Wrocław, Poland

7Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany

University Hospital Ulm, Ulm, Germany

Background: Tumor Treating Fields (TTFields) are an anti-mitotic,

regional treatment modality, utilizing low intensity alternating electric

elds delivered non-invasively to the tumor using a portable medical

device. TTFields are approved by the FDA for the treatment of glioblas-

toma and malignant pleural mesothelioma. In vitro and invivoTTFields

at 150 kHz reduced the proliferative potential of hepatocelluar carcinoma

(HCC) cell lines. Most HCC patients are not amenable to curative ther-

apies and are treated with systemic treatments following failure of local

treatment options. e HEPANOVA EF-30 Phase II trial (NCT03606590)

was a prospective study investigating the ecacy and safety of TTFields

as a treatment option for advanced HCC concomitant with sorafenib. We

present the naly ecacy and saey data of the HEPANOVA trial.

Methods: Patients (N=25) with unresectable HCC not amenable to local

treatment were enrolled in this study. Patients had ECOG score 0-2;

Barcelona clinic liver cancer (BCLC) stage 0-C and measurable disease

per RECIST. Standard sorafenib treatment was administered 400 mg (2 x

200 mg tablets). TTFields (150 kHz) were delivered for 18 hours/day until

local disease progression (RECIST). Clinical follow up was performed

q4w, with CT/MRI scan q12w. Primary end point was overall response

rate (ORR); secondary: in-eld control rate, 12-month progression-free

survival rate 12 month, 1-year OS rate and incidence and severity of

adverse events.

Results: In evaluable patients (N=21), ORR was 9.5% compared to 4.5%

among historical controls (P=0.24). Disease control rate was 76%. No SAEs

were associated with TTFields. In-eld control rate at 1 year was9.5%.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts88

Discussion: Despite poor prognosis in the study population and low

exposure to study treatments versus previous studies, TTFields plus

sorafenib was safe in late-stage HCC patients.

Conclusion: Ecacy outcomes from HEPANOVA are encouraging and

warrant investigation of TTFields ecacy in HCC with a randomized,

controlled study.

Disclosure Statement: e authors declare no conict of interest.

744

Perioperative infections are a negative predictor for overall

survival in patients undergoing surgery for hepatocellular

carcinoma (HCC)

Hannah Oswald1; Sven Loosen1; Tom Luedde1; Wolfram T Knoefel2;

Christoph Roderburg1; Georg Flügen2; Markus Jördens1

1University Hospital Düsseldorf, Department of Gastroenterology, Hepatology

and Infectious Diseases, Düsseldorf, Deutschland

2University Hospital Düsseldorf, Department of General, Visceral and Pediatric

Surgery, Düsseldorf

Background: Hepatocellular carcinoma (HCC) is the most common liver

tumor and is oen dicult to treat due to the accompanying chronic liver

disease. Optimal selection of patients that benet from surgery is di-

cult. e postoperative course is oen complicated due to concomitant

diseases. Pre- and postoperative infections are oen a problem in these

patients who are immunocompromised due to their chronic liver disease.

erefore, we determined the impact of perioperative infections on the

overall survival of patients undergoing HCC surgery.

Methods: 75 patients treated at the Department of Gastroenterology,

Hepatology and Infectious Diseases or Department of General, Visceral

and Pediatric Surgery of the University Hospital Duesseldorf in the last 10

years and undergoing surgery for HCC were included. Using data avail-

able in the patient’s le, occurrence of infections directly before, during

or within the rst 30 days aer surgery was assessed. e postoperative

infections had to have a clear connection to the surgery performed.

Result: In total 75 patients undergoing surgery for HCC were included.

Medium age was 70 years. Median BMI was 26.0kg/m2. Median over-

all survival of our cohort was 455 days. 31 patients had a perioperative

infection, 44 had no infection. Patients with perioperative infection had

a signicantly reduced overall survival compared to patients with no

perioperative infection (360 vs. 1217 days; log rank X2(1): 8.939, p=0.003).

Discussion: We suggest that perioperative infections are a predictive

factor for overall survival in patients undergoing surgery for HCC. is

argues for a strict surveillance and treatment of possible pre- or postoper-

ative infections. Further studies with more patients need to conrm these

ndings and prospective studies are needed to try optimizing periopera-

tive settings regarding prevention of infections in this vulnerable cohort.

Conclusion: Perioperative Infections have an impact on overall survival

in patients undergoing surgery for HCC.

Disclosure Statement: e authors declare no conict of interest

784

Stereotactic body radiotherapy in the treatment of Pancreatic

Adenocarcinoma

Ahmed Gawish; Thomas Brunner

Klinik für Strahlentherapie und Radioonkologie, Magdeburg, Deutschland

Background: Pancreatic cancer is the third leading cause of cancer-re-

lated death in the United States, with a ve-year overall survival of

approximately 8%. e prognosis of advanced local pancreatic cancer is

unfavorable despite progression in therapy. Highly conformal stereotactic

body radiation (SBRT) is a developing alternative.

is research is to investigate feasibility and safety of Stereotactic Body

Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer

(LAPC)

Material and Methods: For our single-institution retrospective study of

patients with pancreatic cancer treated with SBRT between 2018 and 2020,

we identied an improvement in clinical outcomes. e mean dosage was

55 Gy (with a range of 25-66 Gy) delivered in 5-12 doses. Toxicity, overall

survival, and metastasis, as well as the presence of local progression and

RECIST 1.1 response evaluation criteria in solid tumors, were all included

in the endpoint criteria.

Results: Twenty patients were treated, with a median follow-up of nine

months. Patients who received SBRT had unresectable (55%), or border-

line resectable (5 %) disease, medically inoperable (10%), or developed

local recurrence following the Whipple procedure (30%).

e median follow-up was 9 months (range 3-18 months). e actuarial 1

year local control rate was 65 %. e 2-year OS rates was 25 %. e 1-year

freedom from progression was 45 %. Median time to progression was 8

months. Two patients (10%) experienced late gastrointestinal (GI) grade

3 events.

Conclusion: For treating pancreatic cancer, SBRT might be regarded a

promising strategy that provides local control while being linked with a

slightly higher risk of late GI toxicities. It is a more convenient treatment

regimen in a shorter overall treatment time while being better tolerated

by patients.

Disclosure Statement: e authors declare no conict of interest.

786

The ecacy of the stereotactic body radiation treatment in

the management of the cholangiocarcinoma

Ahmed Gawish; Thomas Brunner

Klinik für Strahlentherapie und Radioonkologie, Magdeburg, Deutschland

Background: We provide single-institution results for people with non-

resectable locally advanced cholangiocarcinoma, both with and without

further neoadjuvant stereotactic body radiation treatment (SBRT) and

chemotherapy.

Methods and Materials: Twenty-two consecutive patients with extrahe-

patic or intrahepatic cholangiocarcinoma had SBRT and were retrospec-

tively evaluated between October 2017 and June 2021. No patient was a

candidate for a liver transplantation , however three patients underwent

a complete resection aer SBRT. SBRT was delivered in 12 fractions with

a median dose of 60 Gy. e toxicity of each participant was rated using

the CTC for Adverse Events. Using the Kaplan-Meier technique, overall

survival (OS), time to progression, and local control were calculated.

Results: e median follow-up was 15 months (range 3-29 months). e

actuarial 1 year local control rate was 85 %. e 2-year OS rates was 30 %,

with a median survival of 15.7 months. e 1- and 2-year freedom from

progression was 68% and 45 %, respectively. Median time to progression

was 13 months. 20 patients (90%) experienced some form of acute grade

1-2 toxicity, most commonly fatigue or pain. no patient experienced grade

≥3 toxicity.

Conclusions: When cholangiocarcinoma cannot be surgically removed

or in recurrence situation aer surgery, SBRT may be considered as an

alternative treatment option. It may be used as part of neoadjuvant ther-

apy or as part of denitive treatment in patients with cholangiocarcinoma.

Disclosure Statement: e authors declare no conict of interest.

789

Toxicity of the gallbladder with high-dose ablative-intent

stereotactic body radiotherapy for liver tumors

Ahmed Gawish; Thomas Brunner

Klinik für Strahlentherapie und Radioonkologie, Magdeburg, Deutschland

Purpose: e toxicity of the gallbladder from hypofractionated and ste-

reotactic body radiation treatment is not well recognized (SBRT). In a

retrospective cohort of patients with primary and metastatic liver cancers

undergoing ablative-intent, we reported on gallbladder and bile system

toxicity.

Methods and Materials: Between 2018-2021, 55 Patients underwent

SBRT of liver lesions in our department. e Patients received 56-66 Gy

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 89

in 5-12 fractions. No gallbladder dose constraints were used at treatment,

and gallbladder volumes and dose-volume histograms were created retro-

spectively. Attributable toxicity was dened as cholecystitis or perforation

without preexisting gallbladder disease. Baseline factors were evaluated

using Fisher exact test and the nonparametric K-sample test.

Results: e average duration of follow-up was 18.2 months (range, 3 -36

months).

e biliary system was irradiated with >20 Gy in 45 individuals. Twenty-

ve individuals had their gallbladders irradiated with more than 50 Gy.

Only nine individuals had bile duct stenosis; all had preexisting cholelithi-

asis and received biliary stenting before RT.

Conclusions: We found no link between gallbladder dosage and toxic-

ity and did not approach the maximum tolerable gallbladder dose in this

radiation-treated group. To preserve the gallbladder during ablative and

SBR treatments, we propose not limiting the dosage to the gross tumor

volume.

Disclosure Statement: e authors declare no conict of interest.

809

Beeinussen chronische Pankreatitisvs.

Pankreaskopfkarzinom mit pyloruserhaltender

Pankreaskopfresektion nach Traverso-Longmire

unterschiedlich das postoperative Outcome und die

mikrobielle Besiedelung - Ergebnisse eines tertiären

Zentrums

Henry Ptok1; Ronny Otto2; Ina Tammer3; Aristoteles Perrakis4;

Roland S. Croner4; Frank Meyer4

1Klinik für Allgemein- und Viszeralchirurgie, Ernst-von-Bergmann-Klinikum,

Potsdam, Deutschland

2AN-Intitut für Qualitätssicherung in der operativen Medizin, Otto-von-Guericke-

Universität zu Magdeburg mit Universitätsklinikum, Magdeburg

3Institut für Mikrobiologie, Otto-von-Guericke-Universität zu Magdeburg mit

Universitätsklinikum, Magdeburg, Deutschland

4Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie,

Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland

Operativ-therapeutisch etabliert werden Patienten(Pat.) mit chron.

Pankreatitis (CP) als auch mit Pankreaskoparzinom (CA) einer “pylo-

ruserhaltenden Pankreaskopfresektion n. Traverso-Longmire (PPPD)”

unterzogen, was eine vergl. Analyse der postop. Verläufe erlaubt.

Es wurde die ese aufgestellt, dass Pat. mit CA aufgr. der Schwere der

Tu-Erkrankung einen schlechteren Allg.- sowie Immunstatus vs. Pat. mit

CP aufweisen & sich dies im nachteiligeren frühpostop. Outcome nach

PPPD widerspiegelt.

Mit dem Ziel der Eruierung des Einusses der unterschiedl. Diagnosen

wurde das postop. Outcome aller konsekutiven Patienten, die der OP

zwischen 2002-2015 unterzogen wurden, erfasst & vergleichend aus-

gewertet. Das Outcome wurde durch die allg. & spezielle Morbidität,

die Letalität, SSI & die mikrobielle Besiedelungsrate charakterisiert.

Es wurden 308 operierte Pat. eruiert, von denen n=282 Akten auszuw-

erten waren, davon 192 Fälle mit CA (68,1%) & 90 Fälle mit CP (31,9%).

Überraschend waren die sich ähnelnden speziellen Komplikationsraten

von 45,3% (CA)vs. 45,6% (CP;p=0,97) & die 30-d-Hospital-Letalität,

welche sich mit 3,65% (CA) gegenüber 3,3 % (CP; p=0,591) nur ger-

ing unterschied. Die allg. Komplikationsrate lag bei CA mit 23,4% vs.

14,4% (CP;p=0,082) tendenziell höher. Insgesamt wurden bei CP mit

28,9% aller Pat. potenziell pathogene Keime nachgewiesen, bei CA

waren es 32,8% (p=0,509), die Rate der SSI lag bei 29,7% (CA) & 24,4%

(CP;p=0,361). In der multivariaten Analyse war CA signif. Risikofaktor

f. die Entstehung von SSI (OR: 2,025), die Grunderkrankung hatte

sonst keinen signif. Einuss auf das frühpostop. Outcome. Signif.

Risikofaktoren in der multivariaten Analyse waren außerdem das

männl. Geschlecht für SSI & die mikrobielle Besiedelung sowie intraop.

transfundierte EK‘s für die Letalität, allg. & spezielle Komplikationen.

Anhand dieser Ergebnisse wurde ein teils signif., teils tendenziell neg.

Einuss der Grunderkrankung CA, verglichen mit CP, auf das frühpostop.

Outcome gezeigt, insbes. im Hinblick auf SSI nach PPPD.

Disclosure Statement: e authors declare no conict of interest.

810

optimized PD-L 1 scoring of gastric Cancer - are biopsies able

to map the actual PD-L 1 Status of the entire Tumor?

Birgid Schömig-Markiefka1; Jana Eschbach1; Andreas Scheel1;

Aylin Pamuk2; Josef Ruescho3; Thomas Zander2; Reinhard Büttner1;

Wolfgang Schröder2; Christiane Bruns2; Heike Löser1; Hakan Alakus2;

Alexander Quaas1

1Köln, Pathologie Uniklink Köln, Köln, Deutschland

2Köln, Uniklinik Köln, Köln, Deutschland

3Kassel, Pathologie Nordhessen, Kassel, Deutschland

Purpose: PD-1/PD-L1-Immunotherapy has been approved for gastric

carcinoma. PD-L1 assessment by immunohistochemistry is the principle

biomarker. Are biopsies able to map the actual PD-L1 status of the entire

tumor?

Methods: Whole tumor slides of 56 gastric carcinoma were analyzed to

determine the distribution of PD-L1 positive cells in the entire tumor

areas. Tissue micro arrays with four cores of the tumor surface, which

represents the endoscopically accessible biopsy zone, were built from the

same tumors. e PD-L1 CPS value was determined separately for each

core. Preoperative diagnostic biopsies were available for 22 of the tumors.

PD-L1 prevalence, sensitivity and specicity were analyzed by using the

whole tumor slides as reference scores. Molecular subtyping was per-

formed and related to the PD-L1 status.

Results: 27.3% of cases were PD-L1 negative (CPS <1), 43.6% showed low

PD-L1 expression (CPS ≥1 to <5), 12.7% moderate (CPS ≥5 to <10) and

16.4% strong expression (CPS ≥10).

e biopsies showed best test characteristics if four surface biopsies were

analyzed combined, i.e. the CPS was calculated across all four biopsies.

e prevalence showed a distribution similar to the resection specimens,

sensitivity was 0.73 and specicity 1.0. Using fewer surface biopsies

decreased sensitivity and specicity and caused false-negative classica-

tions. Compared to the TMAs, the preoperative biopsies showed reduced

sensitivity (0,412).

Discussion: e obtained PD-L1 prevalence is consistent with data of

current clinical studies. Calculation of the test characteristics shows that

surface biopsies can be indicative of the true PD-L1 status based on the

resection specimen. However, an adequate number of biopsies is required.

In this study, n=4 biopsies yielded best results.

Conclusion: If at least four biopsies with a total area of about 4.5mm² are

sampled and analyzed combined, results similar to resection specimens

may be obtained.

If the PD-L1 status is determined on biopsy material, ensure a sucient

number of tumor-bearing biopsies.

Disclosure Statement: e authors declare no conict of interest.

812

sex related molecular aspects in gastrointestinal oncology - to

be aware of an emerging eld in oncology

Birgid Schömig-Markiefka1; Alexander Quaas1; Dorothea Wagner2

1Köln, Pathologie Uniklinik Köln, Köln, Deutschland

2Lausanne, lausanne Universtitätshospital (CHUV), Onkologie, Lausanne,

Schweiz

Purpose: e importance of sex and gender as modiers of health, dis-

ease and medicine is increasingly recognized. In fact, sex-related dier-

ences are a reality in multiple facets of oncology, like tumor epidemiology,

molecular biology, tumor immunology, and tumor treatment.

Methods: We used an extensive literature search in Pubmed, Medline, and

Google-Scholar as a basis as well as results of our own analysis in esopha-

geal and gastric carcinomas (n=1100 tumors) are also considered.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts90

Results: Epstein-Barr-Virus-related gastric carcinomas are predomi-

nantly found in male patients, whereas microsatellite-instable tumors in

the distal part of the stomach are found more oen in female patients.

Males develop adenocarcinomas of the esophagus (8-9:1 ratio), whereas

the underlying Barrett’s mucosa occurs in a 2-3:1 ratio.

Discussion: Why is there an increase in poorly cohesive carcinomas of the

gastric corpus predominantly in young women over the past 10 years (so

called CYF-tumor)? Why do sporadic microsatellite instable colon carci-

nomas (MSI) typically develop in older women in the right-sided colon?

How can gender-specic selection of KRAS mutation subtypes in colon

carcinoma be explained (e.g., KRAS G12C occurs disproportionately in

women)?

Conclusion: e aim is to give a good overview of the current state of

knowledge on the subject of sex-related aspects in the tumor biology of

GI-tumors (esophagus, gastric, small- and large bowel) and can help to

raise awareness of this underrepresented topic in oncology.

Disclosure Statement: e authors declare no conict of interest.

814

GP-2250, a novel anti- cancer agent, targets the energy

metabolism of pancreatic tumor cells trough inhibition of

GAPDH involve ROS, AMPK and NFkB

Britta Majchrzak-Stiller1; Marie Buchholz1; Ilka Peters1; Johanna

Strotmann1; Phillip Höhn1; Thomas Müller2; Waldemar Uhl1;

Chris Braumann1

1St. Josef Hospital Universitätsklinikum der Ruhr-Universität Bochum, Klinik für

Allgemein- u. Viszeralchirurgie, Arbeitsgemeinschaft Molekulare und Klinische

Forschung im IFL, Bochum, Deutschland

2 Geistlich Pharma AG , Wolhusen, Schweiz

Background: GP-2250, an oxathiazinan derivative, displayed selective

cytotoxicity against various tumor cells in vitro and in vivo. But the mech-

anism of action still remained unclear. Now, we were able to show that

GP-2250 acts by impairing the energy metabolism of these tumor cells

involving key enzymes like GAPDH and AMPK and transcription factors

like NFkB.

Methods: Using pancreatic cancer cell lines, we assed key enzymes of the

energy metabolism through activity assays, phosphorylation assays, and

Western blot analysis.

Result: GP-2250 is an eective cancer metabolism-based therapeutic

agent. It depletes metabolic energy, largely through inhibition of GAPDH

(glyceraldehyde-3-phosphate dehydrogenase) which is rate limiting for

aerobic glycolysis. us, GP-2250 reduces ATP in a time- and dose-de-

pendent manner and activates the energy-decit sensor AMPK as well as

several downstream targets, which curtail the growth and proliferation of

tumor cells. Additionally, the NFkB pathway was also impaired by strong

reduction of nuclear p65 binding. Cyclin D1, the driver of cell mitosis,

was correspondingly downregulated. Both, metabolic stress and oxidative

stress, through increased ROS levels, contribute to tumor cell death.

Discussion/ Conclusion: GP-2250 is expected to be of wide therapeutic

interest. Its ability to inhibit the provision of metabolic energy, especially

in pancreatic tumor cells, oers a highly promising therapeutic approach.

Disclosure Statement: e authors declare no conict of interest.

884

Stereotactic body radiotherapy for the management of

adrenal gland metastases: a bi-institutional analysis

Felix Ehret1; David Kaul1; Markus Kufeld2; Clara vom Endt1; Volker Budach1;

Christoph Fürweger2; Alfred Haidenberger2; Alexander Muacevic2

1 Charité - Universitätsmedizin Berlin

2 Europäisches Radiochirurgie Centrum

Background: Adrenal gland metastases (AGMs) are a common manifes-

tation of metastatic tumor spread, especially in non-small cell lung cancer

(NSCLC) and small cell lung cancer (SCLC). In patients with a limited

systemic tumor burden, eective treatments for AGMs are needed. Due to

varying fractionation schemes and limited reports, short-course treatment

results for stereotactic body radiotherapy (SBRT) for AGMs are lacking.

is work analyzes the outcomes of short-course SBRT for AGMs.

Methods: Patients who underwent robotic SBRT for AGMs with one to

ve fractions were eligible for analysis.

Result: Data from 55 patients with 72 AGMs from two institutions were

analyzed. Most AGMs originated from renal cell carcinoma (38%) and

NSCLC (35%). e median follow-up was 16.4 months. e median pre-

scription dose and isodose line were 24 Gy and 70%, respectively. Most

patients (85%) received SBRT with just one fraction. e median biologi-

cally eective dose assuming an α/β ratio of 10 (BED10) was 80.4 Gy. e

local control (LC) and progression-free survival aer 1 and 2 years were

92.9%, 67.8%, and 46.2%, as well as 24.3%, respectively. irteen patients

(24%) suered from grade 1 or 2 toxicities. e BED10 showed a signi-

cant impact on LC (p < 0.01). Treatments with a BED10 equal to or above

the median were associated with a better LC (p < 0.01).

Discussion: Results suggest short-course SBRT to be a preferable and

time-saving treatment option for AGMs if an adequate BED10 can be

safely applied. is is in agreement with recent analyses that suggest a

dose-response relationship, with higher BED10 ranging from 80 to over

100 Gy achieving considerable LC rates.

Conclusion: Short-course SBRT is an ecient and safe treatment modal-

ity for AGMs if a sucient BED10 is delivered. Treatment-associated side

eects are sporadic and manageable.

Disclosure Statement: e authors declare no conict of interest.

950

Extended overall survival results from the POLO study of

active maintenance olaparib in patients with metastatic

pancreatic cancer and a germline BRCA mutation

Dirk Arnold1; Pascal Hammel2; Talia Golan3; Michele Reni4;

Eric Van Cutsem5; Teresa Macarulla6; Michael J. Hall7; Joon Oh Park8;

Daniel Hochhauser9; Do-Youn Oh10; Anke Reinacher-Schick11;

Giampaolo Tortora12; Hana Algül13; Eileen M. O’reilly14; Kanu Sharan15;

Xiaoling Ou16; Karen Cui17; Gershon Y. Locker17; Hedy L. Kindler18

1Asklepios Klinik Altona, Hamburg, Deutschland

2Hôpital Paul-Brousse Ap-Hp, Villejuif, Frankreich

3Sheba Medical Center, Tel Aviv, Israel

4San Raaele Hospital, Milano, Italien

5Katholieke Universiteit Leuven, Leuven, Belgien

6Hospital Universitari Vall d’Hebron, Barcelona, Spanien

7Fox Chase Cancer Center, Philadelphia, USA

8Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,

9UCL Cancer Institute, Vereinigtes Königreich

10Seoul National University Hospital, Cancer Research Institute, Seoul,

11St. Josef-Hospital Hörsaal - Katholisches Klinikum Bochum, Bochum,

Deutschland

12Gemelli-Klinik, Roma, Italien

13Klinikum rechts der Isar der Technischen Universität München Notaufnahme,

München, Deutschland

14Memorial Sloan-Kettering Cancer Center, New York, USA

15Merck & Co Inc, Rahway, USA

16AstraZeneca, Milton, Vereinigtes Königreich

17AstraZeneca, Gaithersburg, USA

18University of Chicago, Chicago, USA

Background: e POLO study (NCT02184195) demonstrated a signicant

progression-free survival (PFS) benet for active maintenance olaparib (O)

relative to placebo (P) for patients (pts) with metastatic pancreatic cancer

and a germline BRCA mutation (hazard ratio [HR]: 0.53, 95% condence

interval [CI]: 0.35–0.82; p = 0.004; data cut-o 1 [DCO1]). In the nal

overall survival (OS) analysis (DCO2), the HR for OS favoured olaparib

without reaching statistical signicance (HR: 0.83; 95% CI: 0.56–1.22; p =

0.3487). Here, we present an exploratory extended OS analysis, carried out

12 months aer the nal OS analysis (DCO3).

Methods: Pts (N = 154) were randomized 3:2 to O (300 mg tablets b.i.d.; n

= 92) or P (n = 62). e primary endpoint was PFS by blinded independent

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 91

central review; secondary endpoints included OS, investigator-PFS, time to

treatment discontinuation (TDT) and time to rst and second subsequent

therapies (TFST; TSST). HRs and 95% CIs were calculated using a log-rank

test.

Result: At DCO3, 26 pts (16.9%) remained in the study (O: 20.7%; P:

11.3%). e proportions of pts who remained on O or P were 38.9% vs 9.8%

at 1 year, 24.4% vs 3.3% at 2 years, 16.4% vs 3.3% at 3 years and 13.5% vs

3.3% at 4 years. e OS result at DCO3 remained similar to that at DCO2

(HR: 0.79; 95% CI: 0.55–1.15). However, the KM curves separated clearly

from 24 months aer randomization (estimated O and P survival rates:

34.4% vs 15.7% at 3 years; 23.9% vs 15.7% at 4 years; 19.2% vs 10.5% at

5 years). In total, 7.6% and 27.4% of pts in the O and P arms, respectively,

received a subsequent PARP inhibitor. Investigator-PFS, TDT, TFST and

TSST were longer for O than for P (Table). Safety results were consistent

with DCO2.

Discussion: -

Conclusion: e HR for OS continued to favour O, although the 95% CI

overlapped 1.0. e results indicate an unprecedented durable response to

O in a subset of patients.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

995

Second-Line and Third-Line Therapy with Nanoliposomal

Irinotecan (nal-IRI) in pancreatic cancer: A Single Center

Experience

Christian Möhring1; Freddy José Frontado Grae1; Alexandra Bartels1;

Farsaneh Sadeghlar1; Taotao Zhou1; Robert Mahn1; Milka Marinova2;

Georg Feldmann3; Peter Brossart3; Tim Glowka4; Jörg C. Kal4;

Christian P. Strassburg3; Maria Angeles Gonzalez-Carmona1

1Universitätsklinikum Bonn Medizinische Klinik und Poliklinik I, Bonn,

Deutschland

2Universitätsklinikum Bonn Abteilung für Radiologie, Bonn, Deutschland

3Universitätsklinikum Bonn Medizinische Klinik und Poliklinik III, Bonn,

Deutschland

4Universitätsklinikum Bonn Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-

und Gefäßchirurgie, Bonn, Deutschland

Background: Prognosis of patients with pancreatic cancer (PC) is still

extremely poor. e majority of patients are only suitable for palliative

treatment. In this setting, rst-line palliative therapies with FOLFIRINOX

or gemcitabine/nab-paclitaxel have been established in the last decade. In

the second-line, 5-FU/LV in combination with nanoliposomal irinotecan

(nal-IRI) aer gemcitabine has been shown eective. In this study, we

report about the use of nal-IRI + 5-FU/LV in a daily practice setting in an

unselected cohort of patients with PC and analyzed, whether nal-IRI is an

option as third-line therapy aer prior nonliposomal irinotecan exposure.

Methods: is is a single institution retrospective analysis of patients with

irresectable PC who were treated with nal-IRI and 5-FU/LV from 2017 to

2021 as second- or third-line palliative treatment. Overall survival (OS),

progression-free survival (PFS) and toxicity were analyzed, and multivari-

ate analysis was used to identify independent prognostic factors.

Result: 29 patients receiving nal-IRI and 5-FU/LV were included in the

analysis. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30)

and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients

receiving nal-IRI + 5-FU/LV as third-line treatment (n=19) showed no

OS dierence compared to second-line patients without nonliposomal iri-

noctecan pre-exposure (n=10) (9.33 months vs. 10.27 months; HR: 1.85;

p=0.253). Baseline high CA 19-9 level (HR: 3.281) and metastatic disease

(HR: 7.123) were associated with worse OS. Adverse eects were similar

to reported trials.

Discussion: e use of nal-IRI + 5-FU/LV in unselected patients with

advanced PC showed similar OS, PFS and tolerance as randomized

prospective phase II/III trials. Interestingly, the treatment with nal-IRI

+ 5-FU/LV seemed to be benecial in the third-line therapy despite a

pre-exposure to nonliposomal irinotecan.

Conclusion: Nal-IRI + 5-FU/LV may be considered for patients with

advanced PC, even aer prior nonliposomal irinotecan therapy.

Disclosure Statement: e authors declare the following: Honorare

1001

Characterization of invasive and adhesive behavior of

pancreatic ductal adenocarcinoma cells with dierent cancer

stem cell properties

Arne Surrow1; Umut Ulas Yesilyurt1; Luisa Hattingen1; Amelie Modi1;

Lisa-Marie Philipp1; Susanne Sebens1

1Institut für Experimentelle Tumorforschung Christian-Albrechts-Universität zu

Kiel, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Haus U30/ Eingang

1, Kiel, Deutschland

Background: Pancreatic ductal adenocarcinoma (PDAC) is oen diag-

nosed at advanced stages and oen metastasizes in liver, lung and

peritoneum. During metastasis, PDAC cells undergo epithelial-mesen-

chymal-transition characterized by loss of epithelial and gain of invasive,

mesenchymal phenotype linked to the acquisition of cancer stem cell

(CSC) properties. As own data indicate the existence of mesenchymal and

epithelial CSC phenotypes in PDAC, this study aimed to investigate inva-

sive and adhesion properties of dierent CSC phenotypes.

Methods: Mesenchymal and epithelial PDAC subclones with dierent

CSC properties were characterized. Adhesion of labelled PDAC cells to

liver- and lung endothelial cells as well as mesothelial cells was analyzed

by automated microscopy. For invasion assays, PDAC cells were seeded

into ultra-low-attachment plates for spheroid formation and covered with

Matrigel. Invasive parameters were evaluated with automated microscopy.

Result: Adhesion to mesothelial and lung endothelial cells did not dier

in mesenchymal and epithelial PDAC cells with dierent CSC proper-

ties, but mesenchymal PDAC cells showed a higher adhesion rate to liver

endothelial cells than epithelial PDAC cells. Moreover, PDAC cells with a

mesenchymal CSC phenotype showed the fastest matrix invasion which

occurred in single cells or chains of single cells, while PDAC cells with an

epithelial CSC phenotype invaded much slower in clusters.

Discussion: Mesenchymal and epithelial CSC phenotypes showed dier-

ent invasion modes and adhesion to liver endothelial cells, which is in line

with distinct metastatic patterns in vivo. us, current work investigates

how knockdown of CSC markers impacts invasive behavior of PDAC cell

clones.

Conclusion: ese data indicate that PDAC cells with dierent CSC char-

acteristics dier regarding invasive behavior and putatively metastatic

potential. Future studies identifying determining factors might pave the

way for novel anti-metastatic treatment strategies.

Disclosure Statement: e authors declare no conict of interest.

1002

Carcinoma-associated broblasts and renin-angiotensin

system-based mechanotherapeutics in pancreatic cancer

Sophie He1; Thomas M. Pausch1; Naita Wirsik1; Miriam Schenk1;

Nathalia Giese1; Patrick S. Plum2; Martin Schneider1; Thilo Hackert1;

Thomas Schmidt2

1Universitätsklinikum Heidelberg, Allgemein-, Viszeral- und

Transplantationschirurgie , Heidelberg, Deutschland

2Universitätsklinikum Köln, Allgemein-, Viszeral- und Transplantationschirurgie,

Köln, Deutschland

Background: Pancreatic ductal adenocarcinoma (PDAC) has a pro-

nounced desmoplastic stroma, which plays a central role in poor ther-

apeutic response. Carcinoma-associated broblasts (CAFs) are the most

common stromal cells and of therapeutic interest. Depending on the

subpopulation they have pro- or anti-carcinogenic functions. In col-

orectal cancer, we have shown that renin-angiotensin-aldosterone sys-

tem (RAAS) inhibitors reduce CAF-induced tumor stiness, improving

antiangiogenic therapy and survival. In PDAC we have proved mutual

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts92

stimulation of tumor cells and CAFs in vitro. Further elucidation of the

role of CAFs and stromal mechanics in the context of RAAS inhibitors is

a prerequisite for therapeutic use of these established drugs. e purpose

of this study was the histological analysis of potential modulation of the

desmoplastic stroma by RAAS inhibitors and correlation with survival in

in patients with resected PDAC.

Methods: In tumor tissue of primarily resected PDAC patients (n = 47),

the eect of preoperative administration of RAAS inhibitors on tissue

stiness (Col-1, PMLC), CAF activitation (α-SMA, PDGFRα) and prolif-

eration (Ki67) was examined immunohistochemically. In parallel, clinical

correlation with survival was carried out in univariate and multivariate

analysis.

Results: Histological analysis showed a trend towards negative correlation

of the ratio of CAF activation and stroma stiness, activated stroma index

(ASI), with patient survival (ASI cut-o 0.5, p = 0.1). is correlation was

weaker in patients aer RAAS inhibitor therapy (p = 0.3).

Discussion: Validation on a larger cohort, with primary patient cells

and associated with oncological therapy will follow, in order to optimize

patient selection for possible renin-angiotensin system-based mechanoth-

erapy in PDAC.

Conclusion: RAAS inhibitors have a modulating eect on the desmoplas-

tic stroma in PDAC. is modulation does not seem to aect patient sur-

vival in primary resected PDAC.

Disclosure Statement: e authors declare no conict of interest.

1003

Real-world timelines of BRCA1/2-related molecular testing in

pancreatic cancer

Weiyan LI1; Suvina Amin1; Seongjung Joo2; Gboyega Adeboyeje2;

Patricia Dearbeloa3; Emanuel F Petricoin III3,4; Edik M Blais3;

Michael J Pishvaian3,5

1AstraZeneca, Gaithersburg, USA

2Merck, Kenilworth, USA

3Perthera, Holliston, MA , USA

4George Mason University, Fairfax, USA

5Johns Hopkins School of Medicine, Baltimore, USA

Background: Olaparib is an approved PARP inhibitor (PARPi) for germ-

line BRCA1/2-mutated metastatic PaC. e availability of BRCA1/2 test-

ing results at the time of 1st line and subsequent treatment decisions in the

advanced stage has not been established in real-world settings.

Methods: Longitudinal clinical/molecular data collected between 1/2012-

12/2020 were retrospectively analyzed in 75 PaC pts with germline or

somatic BRCA1/2 mutations (BRCA1/2m) who enrolled in Perthera’s US

real-world observational registry. Tumor NGS testing results were gener-

ated by commercial labs for all patients. Germline status was assessed by

a molecular tumor board when testing results are available. BRCA1/2m

discovery timing (days since advanced presentation), molecular testing

turnaround time (days from physician order to result), and platinum uti-

lization were abstracted from physician records. Associations between

BRCA1/2m discovery timing and platinum utilization were evaluated

using Fisher’s exact test.

Result: At the time of advanced PaC diagnosis, BRCA1/2m status was

known in a minority of patients (29% (22 of 75). In the remaining 71%

(53 of 75) patients, the median time to report BRCA1/2m status was 76

days (IQR=56-558) following advanced diagnosis. e median tumor

NGS testing turnaround time was 35 days aer physician order (IQR=24-

54). Platinum use in any setting was documented in 85% (64 of 75) of

patients and the majority of these patients (62%, 40 of 64) initiated a plati-

num-based regimen before BRCA1/2m status was rst reported. Platinum

agents were initiated before 2nd line in 75% (48 of 64) patients, and this

was associated with BRCA1/2m identication before advanced diagnosis

(p=0.03).

Conclusion: BRCA1/2 testing results may not always be available when

1st line regimens are chosen which can impact ideal treatment sequencing

in PaC patients. ese real-world analyses underscore the importance of

upfront BRCA1/2 testing in PaC patients.

Indication of source:

1 American Society of Clinical Oncology Gastrointestinal Cancer Symposium,

Jan 20-22, 2022

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

1009

Clinical outcome and prognostic factors of pancreatic

adenosquamous carcinoma compared to ductal

adenocarcinoma – results from the nationwide German ADT

registry

Rüdiger Braun1; Louisa Bolm1; Kim Honselmann1; Ekaterina Petrova1;

Hryhoriy Lapshyn1; Steen Deichmann1; Monika Klinkhammer-Schalke2;

Sylke Ruth Zeissig2; Kees Kleihus van Tol3; Benjamin Heckelmann1;

Peter Bronsert4; Sergii Zemskov5; Richard Hummel1; Tobias Keck1;

Ulrich Wellner1

1Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck,

Lübeck, Deutschland

2Netzwerk für Versorgung, Qualität und Forschung in der Onkologie,

Arbeitsgemeinschaft Deutscher Tumorzentren (ADT), Berlin,

3Netzwerk für Versorgung, Qualität und Forschung in der Onkologie,

Arbeitsgemeinschaft Deutscher Tumorzentren (ADT), Berlin, Deutschland

4Institut für Chirurgische Pathologie, Universitätsklinikum Freiburg, Freiburg,

Deutschland

5Department of General Surgery, Bogomolets National Medical University, Kiew,

Ukraine

Background: Adenosquamous carcinoma of the pancreas (ASCP) is a

rare malignancy and it’s pathophysiology is poorly understood. Sparse

clinical data suggest that overall survival is worse in comparison to ductal

adenocarcinoma (PDAC).

Methods: Clinical outcome and prognostic factors for overall survival of

patients with ASCP in comparison to PDAC documented in the nation-

wide registry of the Association of German Tumor Centers were evaluated.

Result: 278 patients with ASCP were identied. Signicantly more

patients underwent surgical resection in the cohort of ASCP patients in

comparison to patients with PDAC (p<0.001). In the cohort of 142 sur-

gically resected patients with ASCP the majority of patients was treated

by a partial pancreatoduodenectomy (44.4%). However, compared to the

cohort of PDAC patients signicantly more patients underwent distal pan-

createctomy (p<0.001). ASCPs were signicantly more oen poorly dier-

entiated (G3) (p<0.001) and blood vessel invasion (V1) was detected more

frequently (p=0.01) in comparison with PDAC. Median overall survival

was 6.13 months (95% CI 5.20 - 7.06) for ASCP and 8.10 months (95% CI

7.93 - 8.22) for PDAC patients (p=0.094). However, when comparing only

those patients who underwent surgical resection, overall survival of ASCP

patients was signicantly shorter (11.80; 95% CI 8.20 – 15.40) compared

to PDAC patients (16.17; 95% CI 15.78 – 16.55) (p=0.007). ASCP was a

highly signicant prognostic factor for overall survival on multivariable

Cox regression analysis (HR 0.767; 95% CI 0.596 - 0.0987; p=0.039).

Discussion: ASCP showed poorer dierentiation and higher frequency of

blood vessel invasion indicative of a more aggressive tumor biology. e

surgical procedures suggest that a signicantly higher proportion of ASCP

tumors was located in the pancreatic body/tail.

Conclusion: ASCP was a negative prognostic factor for overall survival.

Overall survival of resected ASCP patients was signicantly shorter

compared to resected PDAC patients. However, surgical resection still

improves survival signicantly.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 93

1044

MATTERHORN: Ecacy and safety of neoadjuvant-adjuvant

durvalumab and FLOT chemotherapy in resectable gastric

and gastroesophageal junction cancer – a randomized,

double-blind, placebo-controlled, phase 3 study

Yelena Janjigian1; Eric Van Cutsem2; Kei Muro3; Zev Wainberg4;

Salah-Eddin Al-Batran5; Woo Jin Hyung6; Daniela Molena7; Brent Evans8;

Dario Ruscica9; Scott H. Robbins8; Alejandra Negro8; Josep Tabernero10

1Memorial Sloan Kettering, New York,

2University Hospitals Leuven and KULeuven, Leuven, Belgien

3Aichi Cancer Center Hospital, Nagoya, Japan

4David Geen School of Medicine at UCLA, Los Angeles, USA

5University Cancer Center, Frankfurt am Main, Deutschland

6Yonsei University College of Medicine, Seoul, Korea, Dem. People’s Rep. of

7Memorial Sloan Kettering, New York, USA

8AstraZeneca, Gaithersburg, USA

9AstraZeneca, Cambridge, Vereinigtes Königreich

10Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology,

Barcelona, Spanien

Background: Gastric/gastroesophageal junction cancers (GC/GEJC) are

the 5th most common cancers and the 3rd leading cause of cancer-re-

lated deaths globally. Standard of care for resectable GC/GEJC includes

neoadjuvant-adjuvant FLOT chemotherapy with surgery for some

regions of the world. Despite treatment advances, 5-year recurrence rate

remains high and 5-year overall survival (OS) is poor. Evidence suggests

cytotoxic chemotherapy can promote antitumor immunity, thus the

combination of immune checkpoint inhibitors, such as durvalumab (an

anti–PD-L1 antibody), with chemotherapy may result in increased e-

cacy. MATTERHORN (NCT04592913) is a Phase 3, multicenter study

evaluating the ecacy and safety of neoadjuvant-adjuvant durvalumab

or placebo with FLOT followed by adjuvant durvalumab or placebo in

patients with resectable GC/GEJC.

Methods: About 900 adult patients will be randomized 1:1 to Arm A

or B for 2 neoadjuvant and 2 adjuvant cycles (single cycle: durvalumab

or placebo every 4 weeks [Q4W] + FLOT [Q2W × 2]); followed by

durvalumab or placebo Q4W for 10 cycles. Eligible patients must have

histologically conrmed, resectable, Stage II or higher GC or GEJC

untreated with anticancer therapy, ECOG 0 or 1, and adequate organ

function. Key exclusion criteria are any prior immune-mediated therapy,

peritoneal dissemination or distant metastasis, (adeno)squamous cell car-

cinoma, or gastrointestinal stromal tumor. Primary endpoint is event-free

survival assessed by blinded independent central radiology review and/or

local pathology testing. Secondary endpoints include OS and pathological

complete response rate (pCR). Safety and tolerability will be evaluated by

adverse events, vital signs, laboratory parameters, and electrocardiogram.

Enrollment is ongoing.

Funding: AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

1064

Dose-escalation and dose-expansion study of trastuzumab

deruxtecan (T-DXd) monotherapy and combinations in

patients (pts) with advanced/metastatic HER2+ gastric cancer

(GC)/gastroesophageal junction adenocarcinoma (GEJA):

DESTINY-Gastric03

Alexander Stein1; Florian Lordick2; Yelena Y Janjigian3; Do-Youn Oh4;

Keun-Wook Lee5; Neeltje Steeghs6; Yee Chao7; Maria DI Bartolomeo8;

Marc Díez García9; Nadia Haj Mohammad10; William Mcadoo11;

Megan Winter12; Elizabeth Croydon13; Jeeyun Lee14

1Hämatologisch-Onkologische Praxis Eppendorf, Hamburg, Deutschland

2University of Leipzig Medical Center, Leipzig

3Memorial Sloan Kettering Cancer Center, New York, USA

4Seoul National University Hospital, Seoul National University College of

Medicine, Republik Korea

5Seoul National University College of Medicine, Seoul National University

Bundang Hospital

6Netherlands Cancer Institute

7Taipei Veterans General Hospital, National Yang Ming Chiao Tung University,

Section 2

8Fondazione IRCCS Istituto Nazionale dei Tumori

9Vall d’Hebrón University Hospital-VHIO

10University Medical Center Utrecht

11AstraZeneca Pharmaceuticals LP, Gaithersburg

12AstraZeneca Pharmaceuticals LP, Cambridge

13AstraZeneca Pharmaceuticals

14Samsung Medical Center, Sungkyunkwan University School of Medicine,

81, Irwon-ro, Gangnam-gu, Seoul 06351 KR

Background: T-DXd is an antibody-drug conjugate of a humanized anti-

HER2 monoclonal antibody, a tetrapeptide-based cleavable linker, and

a topoisomerase I inhibitor payload. In DESTINY-Gastric01, T-DXd

showed improved ecacy vs SOC in Japanese and Korean pts (≥2 prior

therapies) with advanced HER2+ GC/GEJA. Preclinical data of T-DXd

combinations suggest encouraging antitumor activity. DESTINY-

Gastric03 is the rst study of T-DXd combinations in GC/GEJA.

Methods: DESTINY-Gastric03 (NCT04379596) is a 2-part, phase 1b/2,

multicenter, open-label, 3+3 dose-escalation (part 1) and -expansion

(part2) study. In part 1, pts with locally conrmed HER2+ GC/GEJA

(IHC 3+ or IHC 2+/ISH+) progressed on/aer ≥1 prior therapy including

a trastuzumab-containing regimen received T-DXd every 3 weeks+as-

signed combination. Primary objectives were safety and recommended

phase 2 dose (RP2D). Conrmed objective response rate (ORR) was a

secondary endpoint.

Result: In part 1, 15 pts were assigned to T-DXd+5-FU and 10 pts to

T-DXd+oral capecitabine (Cap). Starting doses were T-DXd 5.4 mg/

kg+5-FU 800 mg/m2 and T-DXd 5.4 mg/kg+Cap 1000 mg/m2 twice daily

(BID). ere were 2 dose-limiting toxicities of grade 3 stomatitis with

T-DXd 6.4 mg/kg+5-FU 800 mg/m2 exceeding maximum tolerated dose,

and was discontinued. RP2Ds were T-DXd 6.4 mg/kg+5-FU 600 mg/m2

and T-DXd 6.4 mg/kg+Cap 1000 mg/m2 BID. Preliminary conrmed and

conrmed + unconrmed ORR at the RP2D for T-DXd+Cap were 3/7

and 5/7

Discussion: -

Conclusion: DESTINY-Gastric03 preliminary part 1 results suggest tol-

erability and feasibility of the RP2Ds for T-DXd+5-FU and T-DXd+Cap.

Preliminary ORR with the T-DXd+Cap RP2D (n=7) showed ecacy with

this combination in heavily pretreated, trastuzumab- and uoropyrimi-

dine-refractory, HER2+ GC/GEJA. is study is ongoing.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts94

1065

Perioperative epidural analgesia has no eect on survival

after partial pancreatoduodenectomy: long-term follow-up of

a multicenter randomized controlled trial

Rosa Klotz1; Maximilian Joos1; Anja Tremmel1; Christopher Büsch2;

Phillip Knebel1; Jan Larmann3

1Department of General, Visceral- and Transplantation surgery, Heidelberg

University Hospital, Heidelberg, Deutschland

2Institute of Medical Biometry, University of Heidelberg, Heidelberg,

Deutschland

3Department of Anesthesia, Heidelberg University Hospital, Heidelberg,

Deutschland

Background: Perioperative thoracic epidural analgesia (EDA) and

patient-controlled intravenous analgesia (PCIA) are frequently used for

pain management aer pancreatic surgery. e PAKMAN trial found that

the occurrence of postoperative gastrointestinal complications does not

dier between perioperative EDA and PCIA aer partial pancreatodu-

odenectomy (PD).1 e purpose of the long-term follow-up (LTFU) of

this study is to compare the two analgesic strategies in terms of recur-

rence-free (RFS) and overall survival (OS).

Methods: e PAKMAN trial was a multicenter, randomized, controlled

superiority trial in which 124 patients with EDA were compared to 124

patients with PCIA aer PD. ree to ve years aer pPD a LTFU was per-

formed and OS, RFS and quality of life were assessed. OS was measured

from the date of pPD until the date of death or censored at last follow-up.

Survival curves were generated using the Kaplan–Meier method and com-

pared between the two intervention groups with the log-rank test.

Result: Data of 111 patients with PCIA and 111 patients with EDA were

available for LTFU. Analysis of OS revealed no signicant dierence

between both groups (p=0.39). Also, subgroup analysis including only

patients with malignant diseases revealed comparable OS.

Discussion: Recent observational studies have found an association

between use of regional anesthesia for cancer surgery and reductions in

disease recurrence. is potential benet of EDA could not be conrmed

in this LTFU of the multicenter randomized controlled PAKMAN trial.

Conclusion: is study found that the choice between PCIA and EDA

for pain control aer pancreatic surgery should not be based on concerns

regarding long-term survival.

Indication of source:

1. Klotz R et al. Gastrointestinal Complications Aer Pancreatoduodenectomy

With Epidural vs Patient-Controlled Intravenous Analgesia: A Randomized

Clinical Trial. JAMA Surg. 2020;155(7):e200794.

Disclosure Statement: e authors declare no conict of interest.

1074

Trastuzumab Deruxtecan (T-DXd) in Patients (Pts)

With HER2-Positive Gastric Cancer (GC) or Gastroesophageal

Junction (GEJ) Adenocarcinoma Who Have Progressed On or

After a Trastuzumab-Containing Regimen (DESTINY-Gastric04,

DG-04): A Randomized Phase 3 Study

Kohei Shitara1; Ferdous Barlaskar2; Fabio A. Franke3; Yoshinori

Kawaguchi2; Lin Shen4; Takahiro Kamio5; Gerold Meinhardt2;

Josep Tabernero6

1National Cancer Center Hospital, Tokyo, Japan

2Daiichi Sankyo, Basking Ridge, NJ, USA

3Hospital Unimed Noroeste, Ijuí, Brasilien

4Beijing Cancer Hospital, Beijing, China, VR

5Daiichi Sankyo, Tokyo, Japan

6Vall d’Hebron University Hospital, Barcelona, Spanien

Background: T-DXd is an antibody–drug conjugate of an anti-HER2

antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I

inhibitor. T-DXd is approved globally to treat HER2+ metastatic breast

cancer, and in the US and Japan to treat advanced HER2+ GC. In the

primary analysis of DESTINY-Gastric01 (NCT03329690), an open-label,

multicenter, randomized, phase 2 trial in pts with HER2+ advanced GC/

GEJ carcinoma, T-DXd showed clinically relevant improvement vs. with

standard of care in objective response rate (ORR; 51% vs 14%; P < 0.001)

and overall survival (OS) benet (12.5 vs 8.4 mo; hazard ratio [HR] 0.59

[95% CI 0.39-0.88]; P = 0.01) in the 3L or later (Shitara, N Engl J Med

2020). e DG-04 study aims to evaluate the ecacy and safety of T-DXd

vs the combination of ramucirumab (ram) and paclitaxel (ptx) in pts with

HER2+ GC/GEJ carcinoma in the 2L setting.

Methods: DG-04 (NCT04704934) is a phase 3, global, multicenter, ran-

domized, open-label study. Eligible pts must be adults, with ECOG status

of 0 or 1, documented GC/GEJ carcinoma previously treated in the met-

astatic 1L setting with a trastuzumab (tmab)-containing regimen. HER2-

positivity (IHC3+ or IHC2+/ISH+) must be centrally conrmed on tumor

biopsies obtained aer progression on or aer tmab. Pts must not have

received anticancer therapy aer a rst-line tmab-containing regimen. Pts

will be randomized 1:1 to T-DXd (6.4 mg/kg every 3 weeks) or ram (8 mg/

kg on days 1 and 15 of a 28-day cycle) with ptx (80 mg/m2 on days 1, 8,

and 15 of a 28-day cycle). DG-04 is actively enrolling with approximately

490 participants planned. Primary endpoint is OS, secondary endpoints

include progression-free survival, ORR, duration of response, disease

control rate, safety, pharmacokinetics, and T-DXd immunogenicity.

Funding: Daiichi Sankyo, Inc., and AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organiser KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 95

Genitourinary Cancer including Prostate Cancer

Best-of-Abstract-Vortrag

556

Clinical and histopathological characterization of penile

carcinomas with focus on HPV-status and histological subtype

Jan Mink1; Oybek Khalmurzaev2; Sebastian Hölters1; Alexey Pryalukhin3;

Julia Heinzelbecker1; Stefan Lohse4; Kristof Bende5; Hagen Loertzer6;

Joachim Steens7; Carmen Jerónimo8; Heiko Wunderlich9; Rainer Bohle3;

Michael Stöckle1; Vsevolod Matveev2; Arndt Hartmann5; Kerstin Junker1;

João Lobo8; Rui Henrique8

1Universitätsklinikum des Saarlandes, Abteilung für Urologie und

Kinderurologie, Homburg, Deutschland

2Federal State Budgetary Institution “N.N. Blokhin National Medical Research

Center of Oncology” оf the Ministry of Health of the Russian Federation,

Department of Urology, Moscow, Russische Föderation

3Universitätsklinikum des Saarlandes, Abteilung für Pathologie, Homburg,

Deutschland

4Universitätsklinikum des Saarlandes, Abteilung für Virologie, Homburg,

Deutschland

5Universitätsklinikum Erlangen, Abteilung für Pathologie, Erlangen, Deutschland

6Westpfalz Klinikum Kaiserslautern, Abteilung für Urologie und Kinderurologie,

Kaiserslautern, Deutschland

7St.-Antonius-Hospital, Abteilung für Urologie und Kinderurologie, Eschweiler,

Deutschland

8Portuguese Oncology Institute of Porto, Porto Comprehensive Cancer Center

(Porto.CCC) & RISE@CI-IPOP (Health Research Network), Porto, Portugal

9St. Georg Klinikum Eisenach, Klinik für Urologie und Kinderurologie, Eisenach,

Deutschland

Background: Most data on prognostic factors for penile cancer (PC) are

based on small cohort sizes, and even meta-analyses are limited in patient

numbers. So in many situations there is a lack of evidence for clinical deci-

sions. About 50% of PC are HPV-associated, but there are conicting data

about the inuence of HPV-status on prognosis.

Methods: Clinical data and tissue samples from 276 patients with PC

from Germany, Russia and Portugal were collected. HPV-Status was

determined by genotyping and p16-immunostaining. Survival data were

analysed by Kaplan-Meier estimator, log rank test and uni- and multivar-

iate analysis using Cox regression model in relation to TNM stage, HPV

and histological subtype.

Result: In multivariate analysis, pN2-3 was signicantly associated with

worse cancer specic (CSS), metastasis free (MFS) and overall survival

(OS) (p = <0.001). Lymphovascular invasion (LVI) was an independent

prognostic parameter for worse CSS (p = 0.005) and OS (p = 0.007),

whereas MFS was signicantly dierent between pT1b and pT1a (p =

0.017). In pN0-patients, LVI was signicant for MFS (p = 0.032). Grading

and perineural invasion were signicant in univariate but not in multivar-

iate analysis. HPV-status was not associated with prognosis. Histological

subtypes dier in prognosis, without reaching statistical signicance.

Discussion: In accordance with literature lymphatic involvement had

the most signicant inuence on prognosis. So the poor prognosis in the

pT1b-group seems to be due to the inclusion of cases with LVI in this

group.

Conclusion: As LVI is a signicant independent prognostic parameter,

the inclusion of tumor-grade and LVI in a single T-category (pT1b) seems

questionable. Histological subtype should always be determined, whereas

HPV-status seems to be of minor clinical relevance. Nodal negative

patients with LVI are on a higher risk of metastasis. erefore, LVI should

be considered as an important factor in the decision making process aer

treatment of the primary tumor.

Disclosure Statement: e authors declare no conict of interest.

Poster

Hypoalbuminemia as a predictor of wound healing disorders

in inguinal lymphadenectomy in the context of penile

carcinoma

Desiree Louise Dräger1, Sophie Groh1, Tim Buchholz1, Oliver Hakenberg1

1Klinik und Poliklinik für Urologie, Universitätsmedizin Rostock, Rostock

Purpose: Inguinal lymphadenectomy is part of the operative management

of penile cancer from stage pT1b. e procedure is associated with wound

healing disorders that can delay the need for chemotherapy. Wound heal-

ing is a complex process that can be prevented by various factors. e

search for disruptive factors with subsequent elimination can, however,

become a successful treatment principle. We investigated hypoalbumin-

emia, as a marker of nutritional status, as a predictor of wound healing

disorders aer inguinal lymphadenectomy.

Material: Preoperative nutritional screening and collection of albumin,

which was correlated with postoperative wound healing disorders aer

inguinal lymphadenectomy in penile cancer patients (n = 89), taking into

account comorbidities, metastasis status and surgical technique.

Results: Wound healing disorders were associated with hypoalbuminemia

(<35 g/l; p = 0.006). Patients without malnutrition had signicantly fewer

postoperative complications (p<0.001). Multivariate analyzes showed that

hypoalbuminemia (p <0.0001), metastasis stage (p=0.004) and surgical

technique (p=0.011) were factors that were independently associated with

a poorer surgical outcome.

Discussion: Inguinal lymphadenectomy is part of the operative manage-

ment of penile cancer. Hypoalbuminemia and malnutrition can predict

impaired wound healing.

Conclusions: Nutritional conditioning prior to tumor surgery can have a

positive eect on the rate of postoperative complications.

Disclosure Statement: e authors declare no conict of interest.

Förderung von klinischen Studien in der Uro-Onkologie durch

die AUO

Heidrun Rexer; Peter Hammerer

Deutsche Krebsgesellschaft e. V., Arbeitsgemeinschaft Urologische Onkologie,

Berlin, Deutschland

Zielsetzung: Unterstützung für die Durchführung von qualitativ hoch-

wertigen Studien im Bereich der Uro-Onkologie.

Methoden: Die Arbeitsgemeinscha Urologische Onkologie (AUO)

der Deutschen Krebsgesellscha hat sich seit ihrer Gründung in

den 90er-Jahren zum Ziel gesetzt, die Durchführung von klinischen

Studien im Bereich der Uro-Onkologie zu fördern. Von Beginn an lag

das Augenmerk auf der hohen Qualität sowie der möglichst raschen

Durchführung der Studien, um die medizinische Versorgung uro-onkol-

ogischer Patienten zu verbessern.

Um hochwertige Studien zu identizieren, hat die AUO einen

Kurzbegutachtungsprozess entwickelt, mit dem die vorgelegten Studien

auf Sinnhaigkeit und Machbarkeit geprü werden. Bei positivem

Studienergebnis unterstützt die AUO die Studiendurchführung durch

verschiedene Maßnahmen, um eine möglichst rasche Rekrutierung

der Studie zu erreichen. Hierfür wird die jeweilige Studie auf der

AUO-Homepage präsentiert und durch Artikel der AUO in mehreren

Fachzeitschrien publiziert. Durch die so erreichte breite Leserscha

können wir die potentielle Zuweisung von geeigneten Patientinnen und

Patienten in die teilnehmenden Studienzentren verbessern.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts96

Ergebnisse/Status: Derzeit werden durch die AUO fast 40 Studien für

die Indikationen Urothelkarzinom, Prostatakarzinom, Hodenkarzinom

sowie Nierenzellkarzinom gefördert. Es wird ein Überblick über die

geförderten Studien gegeben.

Schlüsselwörter: Uro-Onkologie, klinische Studien, AUO

Korrespondenzadresse:

Heidrun Rexer

AUO

Seestr. 11, 17252 Schwarz

AUO@MeckEvidence.de

Disclosure Statement: e authors declare no conict of interest.

Contemporary physician-patient communication formats for

prostate and kidney cancer patients

Andreas Ihrig1

1Klinik für Allgemeine Innere Medizin und Psychosomatik, Universitätsklinik

Heidelberg, Sektion Psychoonkologie, Heidelberg, Deutschland

Background: Diagnostic processes of physicians are characterized by

guidelines and medical knowledge. Treatment decision-making processes

(TD-MP) of patients are oen unstructured and individually dierent.

erefore, the physician -patient conversation has a central importance

for the TD-MP of patients.

Methods: Current needs and experiences of renal and prostate cancer

patients (PCP) are examined in 3 studies in TD-MP and 3 studies exam-

ining contemporary approaches of physician-patient communication.

Result: PCP reported using Internet information and recommendations

from friends as a basis for their TD, in addition to recommendations from

physicians. Only 5.5% of 7169 PCP indicated that they wanted to leave

their TD predominantly to their physician. Participants of an Internet

self-help online forum were signicantly younger and the proportion of

relatives was signicantly higher than in traditional self-help groups. More

than 25% of patients reported that their therapy decision was signicantly

inuenced by the self-help group. Educational talks with multimedia sup-

port before prostatectomy were rated signicantly more positively than

classical talks. Patient participation in renal tumor boards was rated posi-

tively by both patients and physicians.

Discussion: We found patients to prefer a more active participation in

TD-MP compared to previous surveys. Information from the Internet

and recommendations from relatives seem to play an increasing role in

the TD-MP of patients. is information overload could lead to patients

being overwhelmed and including non-valid information in their TD-MP.

Patients might opt for a therapy that does not comply with the guidelines

without being aware of the medical background.

Conclusion: Multimedia elements are a contemporary addition to

the physician-patient conversation. For more complex medical issues,

patients should be given the opportunity to participate in tumor boards.

Experiencing the interdisciplinary exchange strengthens their condence

in the recommendation.

Disclosure Statement: e authors declare no conict of interest.

Sequential treatment patterns over time for advanced renal

cell carcinoma: data from the German research platform

CARAT

Peter J. Goebell1; Carsten Grüllich2; Lothar Müller3; Martin Bögemann4;

Uwe Martens5; Eyck von der Heyde6; Dietmar Reichert7; Arnd Nusch8;

Anke Schlenska-Lange9; Natalie Wetzel10; Michaela Koska10;

Martina Jänicke10; Norbert Marschner11; Michael Staehler12;

Viktor Grünwald13

1Universitätsklinikum Erlangen, Kinderurologie, Urologie, Erlangen, Deutschland

2Universitätsklinikum Carl Gustav Carus Dresden, Urologie, Dresden,

Deutschland

3Onkologie UnterEms Leer-Emden-Papenburg, Dr. L. Müller, Leer, Deutschland

4Universitätsklinikum Münster, Urologie und Kinderurologie, Münster,

Deutschland

5SLK Kliniken Heilbronn, Klinik für Innere Medizin III, Heilbronn, Deutschland

6Onkologische Schwerpunktpraxis, Hannover, Deutschland

7Gemeinschaftspraxis für Hämatologie und Onkologie, Westerstede,

Deutschland

8Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland

9Krankenhaus Barmherzige Brüder, Onkologie und Hämatologie, Regensburg,

Deutschland

10iOMEDICO, Freiburg, Deutschland

11Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg, Deutschland

12Klinikum der Universität München Campus Großhadern, Urologische Klinik

und Poliklinik, München, Deutschland

13Universitätsklinikum Essen (AöR), Innere Klinik, Tumorforschung, Essen,

Deutschland

Background: Multiple novel treatments options have emerged for

advanced renal cell carcinoma (mRCC) including several tyrosine kinase

inhibitors (TKIs), mTOR inhibitors (mTOR), and checkpoint-inhibitors

(CPIs). Here, we analysed changes in sequential treatment patterns over

time since 2008.

Methods: CARAT (NCT03374267) is a prospective, observational, clin-

ical registry, which continues the preceding Tumor Registry Renal Cell

Carcinoma (RCC Registry) in Germany. By April 2022, 2290 patients

(pts) in total have been enrolled with 800 pts since the start of CARAT in

2017. Pts are recruited at start of 1st-line treatment, independent of their

treatment. Details on treatments, patient and tumour characteristics and

patient-reported outcomes are collected. Follow-Up is until death or up to

3 years. For the analyses reported herein, all pts with at least one year of

follow-up (N=1717, start of treatment prior to 31/12/2020, database cut

31/12/2021) were considered.

Result: Of 1717 pts, 50% started a 2nd-line treatment, while 26% died

during 1st-line treatment. For 16% 1st-line treatment was ongoing, 8%

were lost to follow-up.

Pts who died prior to 2nd-line treatment were older (median 72 vs. 68

years) and more oen had poor risk IMDC score (40% vs. 17%) and/or

comorbidities (Charlson-Comorbidity-Index ≥1 41% vs. 31%). At the

time of analysis, 75% of pts with start of treatment since 2018 were alive.

Most frequently used 1st-line strategies have changed from mostly TKI to

both, TKI-only or CPI-based treatments. Up to 2014 the most frequent

1st-2nd-line strategies were TKI-mTORi or TKI-TKI (each 19%). 2015-

2018, the sequence TKI-CPI became more frequent (29%) than TKI-TKI

(12%). In 2020 the most common strategies were CPI or CPI+TKI in

1st- and TKI in 2nd-line therapy (7 or 6%) or TKI in 1st-line and CPI in

2nd-line therapy (5%).

Conclusion: Sequential treatments of pts with mRCC are changing show-

ing that novel treatment options are quickly implemented into routine

care in Germany. With longer follow-up, we will provide valuable addi-

tional evidence to guide treatment strategies in the future.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 97

Cabozantinib in adult patients with advanced renal cell

carcinoma following prior systemic checkpoint inhibition

therapy: a retrospective, non-interventional study

Viktor Grünwald1; Martin Bögemann2; Reza Rafyian3; Günter Niegisch4;

Marco Schnabel5; Anne Flörcken6; Michael Maasberg7; Christoph Maintz8;

M.-O. Zahn9; Anke Wortmann10; Andreas Hinkel11; Jochen Casper12;

Christopher Darr13; Thomas Hilser1; Matthias Schulze14; Disorn Sookthai15;

Caroline Schönherr15; Philipp Ivanyi16

1Universitätsklinikum Essen (AöR), Westdeutsches Tumorzentrum Essen, Innere

Klinik (Tumorforschung), Essen, Deutschland

2Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Müster,

Deutschland

3Krankenhaus Nordwest gGmbH, Institut für Klinisch-Onkologische Forschung

(IKF), Frankfurt, Deutschland

4Universitätsklinikum Düsseldorf, Klinik für Urologie, Konservative Urologische

Onkologie, Düsseldorf, Deutschland

5Klinik für Urologie der Universität Regensburg am Caritas-Krankenhaus St.

Josef, Regensburg, Deutschland

6Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie,

Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin,

Deutschland

7Institut für Versorgungsforschung, Mayen, Deutschland

8MVZ West GmbH Würselen, Würselen, Deutschland

9MVZ Onkologische Kooperation Harz, Goslar, Deutschland

10Onkologiezentrum Soest-Iserlohn, Medizinisches Versorgungszentrum GbR,

Soest-Paradiese, Deutschland

11Franziskus Hospital Bielefeld, Onkologisches Zentrum, Bielefeld, Deutschland

12Klinikum Oldenburg AöR, Universitätsklinik für Innere Medizin - Onkologie und

Hämatologie, , Oldenburg, Deutschland

13Universitätsklinikum Essen Klinik für Urologie, Essen, Deutschland

14Praxis Dr. Schulze, Markkleeberg, Deutschland

15Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Deutschland

16Medizinisch Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,

Onkologie und Stammzelltransplantation, Hannover, Deutschland

Background: With the current 1st line shi towards IO-combinations, e-

cacy and safety data of subsequent therapies remains scarce. Cabozantinib

is a standard of care, but data aer IO-failure remains anecdotal. erefore,

primary aim was to evaluate safety and eectiveness of cabozantinib aer

failure of IO-based therapies.

Methods: Data was collected retrospectively from sites in Germany.

Patients (pts) with advanced or metastatic renal cell carcinoma (mRCC)

were eligible. Cabozantinib treatment directly aer failure of IO-based

therapy was mandatory. AEs were reported according to CTCAE 5.0.

Objective response rate according to RECIST 1.1 and Progression Free

Survival (PFS) were collected from medical records. Descriptive statistics

and KM-plots were utilized, where appropriate.

Result: is preliminary analysis (cut o 30-Apr-21) assessed 56 eligible

pts (71.4% male) with median age of 66 yrs. Clear cell RCC was reported

in 66.1% (n=37) and nephrectomy in 87.5% (n=49). 87.5% (n=49) had

≥2 previous lines. ECOG ≤1 was 32.1% (n=18). IMDC factors were 0 in 3

(5.4%), ≥1 in 20 (35.7%), missing in 33 pts (58.9%). 62.5% (n=35) started

at reduced dose. 53.6% (n=30) required dose reductions, 7.1% (n=4)

interruptions and 14.3% (n=8) discontinuation of cabozantinib. PR was

reported in 10.7% (n=6), SD in 19.6% (n=11), PD in 12.5% (n=7) and

missing in 57.1% (n=32). Median treatment duration was 5.9 months and

median PFS was 6.64 months (95% CI 4.99, 8.71). AEs were reported in

87.5% (n=49) and 42.9% (n=24) had grade 3-5. Fatigue (33.3%), diarrhea

(31.7%) and hand-foot-syndrome (23.3%) were the 3 most frequent AEs

of any grade and causality. SAE were reported in 21.4% (n=12), 2 were

fatal.

Discussion: Cabozantinib followed directly aer IO therapy was tolerated

and feasible. No new safety signals were reported. A lower starting dose

was frequently utilized in this real-world cohort of RCC pts but was asso-

ciated with a favorable tolerability prole.

Conclusion: Our data supports the use of cabozantinib aer IO-failure.

Major limitation was the retrospective data capture in our study.

Disclosure Statement: e authors declare no conict of interest.

101

Primary radio(chemo)therapy for inoperable muscle-invasive

bladder cancer – long term results and patterns of care in a

single institution

Laura Anna Fischer1; Leif Hendrik Dröge1; Sandra Donath1;

Stephanie Bendrich1; Jacqueline Possiel1; Markus Schirmer1; Martin Leu1;

Manuel Guhlich1; Andrea Hille1; Stefan Rieken1; Rami El Shae1

1Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,

Göttingen, Deutschland

Background: Radical cystectomy (RC) is the standard of care for mus-

cle-invasive bladder cancer (MIBC). In selected patients, bladder-sparing

trimodal therapy (TMT) can be considered as an alternative treatment,

potentially improving quality of life.

Methods: Between 1998 and 2021, 66 patients received denitive radio-

therapy for inoperable bladder cancer at the University Medical Center

Göttingen. Normofractionated external beam radiotherapy was delivered

at a median total dose of 50,4 Gy (Q1–Q3: 50,3–50,4 Gy) to the blad-

der, including limited pelvic lymph nodes in 40 (87%) cases. A sequential

boost to the primary was delivered at a median total dose of 55,8 Gy (Q1-

Q3: 55,8–59,4 Gy).

Following ethics committee approval, data was retrieved from the patients’

medical and legal records. Patient characteristics, disease prole, treat-

ment pattern, response and OS are analyzed by the methods of Kaplan-

Meyer and log-rank test.

Results: Median patient age was 79,5 years (Q1–Q3: 69,25–84 years).

Of 72 patients, 46 were treated with curative intent, 44 patients under-

went transurethral resection of bladder tumor followed by radiation,

18 patients received a concurrent radiosensitizing chemotherapy (plati-

num-based (n=17) or mitomycin C plus 5-uorouracil (n=1)). Treatment

was discontinued in 5 patients due to a tumor associated deterioration

of general condition, one patient died. Long-term follow-up showed a

decline in bladder function in 43% (e.g. dysurea, pollakisurea), 15% had

an inoperative bladder, only one patient underwent a salvage cystectomy.

2- and 5-year overall survival rates were 59% and 29%, in the TMT sub-

group 75% and 43%.

Conclusion: Radio(chemo)therapy for the treatment of bladder cancer is

safe and feasible and potentially benecial, especially for elderly patients

regarding bladder preservation and avoidance of morbidity or mortality

of RC.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts98

128

Thrombospondin-2 and LDH: potential predictive biomarkers

for the treatment of metastatic renal cell carcinoma

with everolimus after one VEGF-targeted therapy

(MARC-2 study)

Philip Zeuschner1; Sebastian Hölters1,2; Michael Stöckle1; Barbara Seliger3;

Anja Müller3; Hagen S Bachmann4; Viktor Grünwald5,6; Daniel C

Christoph7,8; Arnulf Stenzl9; Marc-Oliver Grimm10; Fabian Brüning11;

PeterJ. Goebell12; Marinela Augustin13; Frederik Roos14,15; Johanna Harde16;

Iris Benz-Rüd16; Michael Stähler17; Kerstin Junker1

1Saarland University, Department of Urology and Paediatric Urology, Homburg/

Saar, Deutschland

2Ingenieurbüro für Gesundheitswesen GmbH, Leipzig, Deutschland

3Insitute of Medical Immunology, Martin Luther University Halle-Wittenberg,

Halle (Saale), Deutschland

4Institute of Pharmacology and Toxicology, Center for Biomedical Education

an Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke

University, Witten, Deutschland

5University Hospital Hannover Medical School , Department of Hematology,

Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Deutschland

6University Hospital Essen, West German Cancer Center, Clinic for Internal

Medicine (Tumor Research) and Clinic for Urology, Essen, Deutschland

7University Hospital Essen, Department of Medical Oncology, Essen,

Deutschland

8Evangelische Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung Essen-

Huttrop, Department of Medical Oncology & Hematology, Essen, Deutschland

9University Hospital Tübingen, Department of Urology, Tübingen, Deutschland

10University Hospital Jena, Department of Urology, Jena, Deutschland

11Philipps-University Marburg, University Hospital Giessen and Marburg GmbH,

Department of Urology and Pediatric Urology, Marburg, Deutschland

12University Hospital Erlangen, Ambulatory Uro-Oncological Therapy Unit

Erlangen (AURONTE), Department of URology and Clinic for Haematology and

Internistic Oncology, Erlangen, Deutschland

13Klinikum Nuremberg, Paracelsus Medical University, Department of

Hematology and Oncology, Nürnberg, Deutschland

14University Medical Center Mainz, Departmet of Urology and Paediatric

Urology, Mainz, Deutschland

15University Hospital Frankfurt, Department of Urology, Frankfurt, Deutschland

16iOMEDICO, Medical Department, Freiburg im Breisgau, Deutschland

17Ludwig-Maximilians-University of Munich, Department of Urology,

Interdisciplinary Center of Renal Tumors, München, Deutschland

Background: e phase IV MARC-2 trial searched for predictive blood

biomarkers in patients with clear cell metastatic renal cell carcinoma

(mRCC) treated with everolimus 2nd line. In an exploratory approach,

the relation of potential biomarkers to clinical endpoints was assessed.

Methods: e expression of 55 angiogenesis-related proteins at C1D1 and

C1D15 were screened by antibody arrays and validated by ELISA in 63

patients. ree metabolic molecules and 4 SNPs in the mTOR gene were

analyzed. Cut-os were calculated with ROC analysis, the survival was

assessed with Kaplan Meier curves and multiple Cox regressions.

Result: Lower levels of angiogenesis-related protein thrombospon-

din-2 (TSP-2) at baseline (≤ 665 parts per billion, ppb) identied ther-

apy responders with longer median progression-free survival (PFS, 6.9

months vs. 1.8, p=0.005). Two weeks aer treatment initiation, responders

had higher LDH (>27.14nmol/l) associated with longer median PFS (3.8

mo vs. 2, p=0.013) and overall survival (OS, 31.0 mo vs. 14.0, p<0.001).

Baseline TSP-2 levels were a stronger independent baseline predictor for

PFS (HR 0.22, p=0.001) than patient characteristics. mTOR polymor-

phisms had a tendency to be associated with therapy response, but were

not signicant.

Discussion: Especially in 2nd and later treatment lines in mRCC, choosing

the optimal drug for each patient remains an unsolved challenge. Blood

biomarkers could serve as minimally-invasive predictive or on-treatment

indicators, whether to continue or change the regimen.

Conclusion: Low baseline thrombospondin-2 and high lactate dehydro-

genase two weeks aer therapy initiation identied patients with longtime

responses to everolimus, which could further increase the response rates

based on individual patient selection.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

149

Episensitation of Cisplatin-Resistant and Naïve Urothelial

Carcinoma Cells towards PARP Inhibitor Treatment

by BET-Inhibitor PLX51107

Anna L. Bartkowiak1; Leandra Lepping1; Sophia Thy1; Sarah Meneceur1;

Patrick Petzsch2; Karl Köhrer2; Michèle Homann1; Günter Niegisch1

1Klinik für Urologie, Heinrich-Heine-Universität Düsseldorf, Medical Faculty,

Düsseldorf, Deutschland

2Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-

Universität Düsseldorf, Medical Faculty, Düsseldorf, Deutschland

Background: Since muscle-invasive urothelial carcinoma (UC) frequently

develop cisplatin resistance new therapeutic options are urgently needed.

Previously, we reported about the bromodomain protein inhibitor (BETi)

PLX51107 (PLX) inducing DNA damage and repair (DDR) deciency

in UC cell lines (UCC), a state also called BRCAness, that is sensitive to

PARP inhibition in other entities. Since Cisplatin-resistant sublines of

UCC (LTTs) are highly dependent on DDR and apoptosis resistance, we

characterized response of LTTs and treatment naïve parental cells towards

combined treatment with PLX51107 and the PARP inhibitor (PARPi)

Olaparib.

Methods: Transcriptomic changes by PLX treatment were detected by

RNA sequencing of two UCC (VM-CUB1 and UM-UC-3) and the benign

control cell line HBLAK. Dierentially expressed genes regulating DDR

and apoptosis were further analysed in transcriptomic proles of three

dierent LTT sublines (RT-112, T-24, J82) compared to their parent cell

lines. Treatment response towards PLX and PARPi Olaparib mono treat-

ment as well as the combination was investigated in named UCC and

HBLAK by MTT assay.

Results: Induction of DDR deciency by PLX and altered expression of

apoptosis regulators was conrmed by qRT-PCR. Factors that may deter-

mine treatment response of UC cells towards BETi and PARPi were iden-

tied. Combination treatment was highly synergistic in LTTs and parental

cell lines, allowing extensive dose reduction. Synergistic eects were con-

rmed by ow cytometry (apoptosis) and clonogenic assays. Combination

of the PARPi with Cisplatin instead of the BETi did not exert synergistic

eects in cisplatin resistant cells.

Discussion: Synergistic treatment with the BETi PLX51107 and the

PARPi Olaparib strongly reduced viability of cisplatin-resistant and –sen-

sitive UCC, but spared normal cells.

Conclusion: Applicability of PARPi may be extended to BRCA wild-type

cancer patients by episensitation with PLX51107. us, this combination

could be a promising therapeutic option for UC also for second line treat-

ment aer chemotherapy.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 99

151

Role of prior nephrectomy for synchronous metastatic renal

cell carcinoma (mRCC) on ecacy in patients treated with

avelumab + axitinib (A + Ax) or sunitinib (S): results

from JAVELIN Renal 101

Marc-Oliver Grimm1; Mototsugu Oya2; Toni K Choueiri3;

Manuela Schmidinger4; David Quinn5; Gwenaelle Gravis-Mescam6;

Elena Verzoni7; Alfonsus Van den Eertwegh8; Alessandra DI Pietro9;

Mariangela Mariani9; Jing Wang10; Despina Thomaidou11;

Laurence Albiges12

1Universitätsklinikum Jena - Klinikum Lobeda, Jena, Deutschland

2Keio University School of Medicine, Tokyo, Japan

3Dana-Farber Cancer Institute, Boston, USA

4Medical University of Vienna, Vienna, Österreich

5Keck School of Medicine USC, Los Angeles, USA

6Institute Paoli-Calmettes, Marseille, Frankreich

7Istituto Nazionale dei Tumori | Fondazione IRCCS, Milano, Italien

8VU University Medical Center, Amsterdam, Niederlande

9Pzer SRL, Milan, Italien

10Pzer, Cambridge, USA

11Pzer, Athens, Griechenland

12Gustave Roussy Cancer Campus, Villejuif, Frankreich

Background: Cytoreductive nephrectomy (neph) remains controversial

in the management of mRCC; the role of neph before immune checkpoint

inhibitor treatment is unknown. In this follow-up analysis of the phase 3

JAVELIN Renal 101 trial (NCT02684006), we assessed the role of prior

neph in patients (pts) with mRCC with synchronous metastases at diag-

nosis treated with A + Ax or S.

Methods: Ecacy outcomes were assessed from the third interim analysis

in pts with mRCC who had M1 disease at diagnosis and had prior neph

or no neph in the A + Ax and S arms. Multivariate Cox regression analy-

ses were used to assess hazard ratios (HRs) for overall survival (OS) and

progression-free survival (PFS; investigator assessment per RECIST 1.1).

Logistic regression was used to obtain odds ratios for objective response

(OR; investigator assessment per RECIST 1.1).

Results: 412 of 886 pts in JAVELIN Renal 101 had M1 disease at diagnosis,

of which 126 (A + Ax) and 147 (S) had prior neph, and 72 (A + Ax) and 67

(S) had no neph. A higher proportion of pts in the no neph vs prior neph

group were older (42% vs 32% were ≥65 years), had impaired PS (ECOG

PS 1, 54% vs 40%), and had poor prognosis (40% vs 16% by IMDC cri-

teria); fewer pts had PD-L1+ tumors (40% vs 77%). To assess the impact

of prior neph, these parameters were adjusted in the multivariate model.

Post hoc analyses showed that in the A + Ax arm, observed PFS and OS

were numerically improved in the prior neph vs no neph group (PFS, HR

[95% CI] 0.785 [0.531-1.161]; OS, HR 0.593 [0.379-0.930]); however, no

dierences were observed in the S arm (PFS, HR 1.146 [0.773-1.699]; OS,

HR 0.859 [0.551-1.341]. Conrmed OR was numerically longer in pts

with neph vs no neph in the A + Ax arm (odds ratio 2.669 [1.315-5.414])

but not in the S arm (odds ratio 2.018 [0.824-4.941]).

Discussion/Conclusions: Pts who had M1 disease at diagnosis and prior

neph had numerically improved ecacy outcomes vs no neph with A +

Ax but not with S.

Previously presented at ESMO 2021, “FPN: 665P”, “Marc O. Grimm etal.”

- Reused with permission

Disclosure Statement: e disclosures are included in the abstract document

152

Final results on ecacy and patient reported outcomes (PRO)

of a randomized phase II trial investigating nivolumab

switch-maintenance after TKI induction in metastatic

clear cell renal cell carcinoma (mRCC) patients (NIVOSWITCH)

Christopher Darr1; Stefanie Zschäbitz2; Philipp Ivanyi3; Manfred Wirth4;

Peter Staib5; Martin Schostak6; Lothar Müller7; Michael Metz8;

Lothar Bergmann9; Thomas Steiner10; Anja Lorch11; Philipp Schütt12;

Mohammad-Reze Rayan13; Eva Hellmis14; Axel Hinke15; Martin Mänz16;

Johannes Meiler17; Thomas Kretz18; Anne Flörcken19; Viktor Grünwald20

1Klinik für Urologie, Universitätsmedizin Essen, Essen, Deutschland

2Klinik für Medizinische Onkologie, Universitätsklinikum Heidelberg,

Deutschland

3Medizinische Hochschule Hannover (MHH) Klinik für Hämatologie,

Hämostaseologie, Onkologie und Stammzelltransplantation, Hannover,

Deutschland

4Klinik für Urologie, Universitätsklinikum Dresden

5Klinik für Hämatologie und Onkologie, St. Antonius Hospital Eschweiler

6Klinik für Urologie, Universitätsklinikum Magdeburg

7Onkologie Untere Ems

8Gemeinschaftspraxis Hämatologie / Onkologie , Göttingen

9Hämatologie / Onkologie, Frankfurt am Main, Deutschland

10Klinik für Urologie, Helios Klinikum Erfurt

11Klinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich

12Onkologische Gemeinschaftspraxis Gütersloh

13Klinik für Onkologie und Hämatologie, Krankenhaus Nordwest, Frankfurt

14Urologicum Duisburg, Duisburg

15Cancer Clinical Research Consulting, Düsseldorf

16Clinical Oncology Resources Berlin GmbH, Berlin

17Hämatologie / Onkologie, Klinik Dr. Hancken

18Urologie Heinsberg

19Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und

Tumorimmunologie, Charite Universitätsmedizin Berlin

20Klinik für Urologie und Innere Klinik Tumorforschung, Universitätsklinik Essen

Background: In mRCC patients (pts) combinations of checkpoint inhib-

itors (CPI) and tyrosine kinase inhibitors (TKI) are considered standards

of care. Our study investigated a 1st line switch-maintenance approach

(CPI aer TKI) to improve outcome in mRCC.

Methods: 49 pts. with partial remission (PR) or stable disease (SD) aer

12 weeks TKI induction therapy were 1:1 randomized to receive either

TKI continuation (24 pts.) or nivolumab (NIVO; 25 pts.; 240 or 480 mg

IV q2-4wk). Data base was closed 12/2020. Pts. with ECOG 0-2 and ade-

quate organ function were permitted. Objective response rate (ORR), pro-

gression free survival (PFS) and adverse events (AE, according to CTCAE

v4.03) were assessed from time of randomization. PRO were assessed by

the FACT Kidney Symptom Index (FKSI-15), with Time to deterioration

(TTD) dened as time between randomization to PRO decrease ≥3 points.

Result: Median age was 65 years, 82% were male and 4% had ECOG

2. Main metastatic sites were lung (47%), lymph nodes (27%) and liver

(24%). Response to TKI induction therapy was PR in 59% and SD in 41%

of pts. PFS was 3.0 vs. 11.9 mo. (HR = 2.57 [95% CI: 1.36 – 4.89]) in favor

for TKI continuation. e median OS was not reached. 2-year OS was

64% for NIVO and 66% for TKI treatment (HR = 1.12 [95% CI: 0.43 –

2.89]; P=0.82). ORR from randomization favored TKI continuation (16

vs. 48%; P=0.03). Aer a median follow-up of 26.3 mo (1.3-45.6), 40 PFS

events and 17 deaths occurred. AEs for NIVO vs. TKI occurred in 96% vs.

100%, grade 3-5: 56% vs. 71% and serious AE: 48% vs. 50%, respectively.

Median FKSI15 score showed no dierence, 46 and 47 for NIVO as well

as for TKI with 42 and 43. Median TTD favored NIVO (NR) vs. TKI (6.9

mo), but dierence remained insignicant (P=0.16).

Discussion: Although a lower degree of grade ≥3 AEs for NIVO was

observed, a PRO benet was not detected. A major limitation is the small

sample size and the selection of TKI-sensitive pts.

Conclusion: Our data do not support the use of a switch-maintenance

approach in mRCC.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts100

153

A prospective, open-label, multicenter, randomized phase

II trial: Sequential therapy with BEvacizumab, RAd001

(Everolimus) and AxiTinib in metastatic renal cell carcinoma

(mRCC) (BERAT study of the IAG-N)

Thomas Hilser1; Viktor Grünwald1; Lothar Bergmann2; Peter J. Goebell3;

Arne Strauß4; Johannes Meiler5; Arndt Hartmann6; Philipp Ivanyi7;

Jens Bedke8

1Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik

(Tumorforschung), Essen, Deutschland

2Universitätsklinikum Frankfurt, Med. Klinik II für Hämatologie/ Onkologie,

Frankfurt am Main, Deutschland

3Universitätsklinikum Erlangen, Klinik für Urologie, Erlangen, Deutschland

4Universitätsmedizin Göttingen, Klinik für Urologie, Göttingen, Deutschland

5Klinik Dr. Hancken GmbH, Stade, Deutschland

6Universitätsklinikum Erlangen, Pathologisches Institut, Erlangen, Deutschland

7Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,

Onkologie und Stammzelltransplantation, Hannover, Deutschland

8Universitätsklinikum Tübingen, Klinik für Urologie, Tübingen, Deutschland

Background: Inhibitors of the vascular endothelial growth factor or its

receptor (TKI) and mammalian target of rapamycin (mTORi) are com-

ponents of the targeted treatment landscape in mRCC. We compared the

2nd line ecacy of TKI and mTORi in mRCC aer failure of bevacizumab/

interferon in a phase II trial.

Methods: Key inclusion criteria were: measurable mRCC , ECOG 0-1,

IMDC risk: good or intermediate, adequate organ function. Patients who

progressed on or were intolerant to BEV/IFN were subject for random-

ization between VEGFRi and everolimus (EVE) treatment. Cross-over

occurred at time of progression during 2nd line treatment. Improvement

of 2nd line PFS-rate at 6 mo. from 50% to 65% was the primary endpoint.

Secondary endpoints were PFS, total PFS, ORR, OS, safety and HR-QoL.

Result: A total of 22 of 100 patients were included between Novmeber

2012 and June 2015 and at that time stopped for poor accrual. 10 patients

(46%) were randomized to receive 2nd line treatment with everolimus

(n=5) or Axitinib (n=4)/ Sunitinib (n=1). Objective response rate was

20% under 1st line treatment with Bev/IFN. Severe adverse events (SAE)

occurred in 60% each arm. ORR was 1/5 (20%) for TKI and 0/5 (0%) for

Everolimus. PFS rate at 6 mo. was 20 % in each arm. Median PFS was 3.7

mo. (EVE) and 2.2 mo. (VEGFRi) [HR 1.0 (95%-CI: 0.26-3.85; p=0.997)].

e OS was comparable between arms HR 1.12 (95%-CI: 0.27-4.61; p=

0.872). e HR-Qol was comparable between arms, too. e data will be

shown. 7 patients crossed over to 3rd line treatment.

Discussion: e rapid change of the treatment landscape, the limited use

of BEV/IFN in 1st line and the duration of 1st line treatment jeopardized

BERAT trial recruitment. e small number of patients is a major limita-

tion of our trial. Our observation indicated the principle poor prognosis

in progressive patients and the limited ecacy of axitinib, sunitinib or

everolimus in 2nd line treatment. Clearly, more ecient 2nd line therapies

are needed.

Conclusion: No major dierences for PFS rates at 6 mo. were detected,

indicating the limited activity of EVE or tested TKIs in 2nd line.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

158

An ongoing, randomized phase II study of Nivolumab

plus Ipilimumab versus standard of care in previously

untreated and advanced non-clear cell renal cell carcinoma

(SUNIFORECAST)

Marit Ahrens1; Bernard Escudier2; John Haanen3; Ekaterini Boleti4;

Marine Gross-Goupil5; Marc-Oliver Grimm6; Sylvie Negrier7;

Philippe Barthélémy8; Gwenaelle Gravis9; Philipp Ivanyi10; Jens Bedke11;

Daniel Castellano12; Andrej Panic13; Begona Mellado14; Pablo Maroto15;

Sylvie Rottey16; Stefanie Zschäbitz17; Anne Flörcken18; Martin Bögemann19;

Tom Waddell20; Cristina Suárez Rodríguez21; Anja Lorch22;

Dorothee Deckbar23; Arndt Hartmann24; Lothar Bergmann1

1University Hospital Frankfurt, Medical Clinic II, Hematology and Oncology,

Frankfurt, Deutschland

2Institut Gustave Roussy, Paris, Frankreich

3Netherlands Cancer Institute, Amsterdam, Niederlande

4Royal Free London NHS Foundation Trust, London, Vereinigtes Königreich

5Cente Hospitalier Universitaire, Bordeaux, Frankreich

6University Hospital Jena, Clinic for Urology, Jena, Deutschland

7Centre Leon Berard, Lyon, Frankreich

8Les Hôpitaux Universitaire de Strasbourg, Strasbourg, Frankreich

9Institut Paoli Calmettes, Clinic for Oncology, Marseille, Frankreich

10Hanover Medical School, Comprehensive Cancer Center Lower Saxony,

Department of Hematology, Hemostasis, Oncology and Stem Cell

Transplantation, Hannover, Deutschland

11University Hospital Tübingen, Clinic for Urology, Tübingen, Deutschland

12Hospital Universitario 12 de Octubre, Clinic of Oncology, Madrid, Spanien

13University Hospital Essen, Northwest German Cancer Center, Clinic for Urology,

Essen, Deutschland

14Hospital Clinic de Barcelona, Clinic for Oncology, Barcelona, Spanien

15San Pau Hospital, Barcelona, Spanien

16University Hospital, Gent, Belgien

17University Hospital Heidelberg, National Center for Cancer (NCT), Clinic for

Oncology, Heidelberg, Deutschland

18Charité Berlin, Berlin (Campus Virchow-Klinikum), Medical Clinic for

Hematology/Oncology and Tumorimmunology, Berlin, Deutschland

19University Hospital Münster, Clinic for Urology, Münster, Deutschland

20Christie NHS Foundation Trust, Manchester, Vereinigtes Königreich

21Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus,

Medical Oncology, Vall d’Hebron Institut of Oncology (VHIO), Barcelona, Spanien

22University Hospital Düsseldorf, Clinic for Oncology, Düsseldorf, Deutschland

23University Hospital Frankfurt, Frankfurt, Deutschland

24Institute for Pathology, University Hospital Erlangen, Erlangen, Deutschland

Background: e heterogenous group of non-clear cell renal cell carci-

nomas (nccRCC) accounts for approximately 25% of RCC patients (pts).

Data on treatment strategies are still limited, since most clinical trials focus

on clear-cell RCC. Recently dierent combination therapies with immune

checkpoint inhibitors (IO) and tyrosine kinase inhibitors (TKI) have

been approved for treatment in RCC independent of the International

Metastatic RCC Database Consortium (IMDC) risk group. In addition,

Nivolumab and Ipilimumab (IO/IO) has been approved for treatment

of intermediate and high-risk pts showing a signicant improvement in

overall response rate (ORR), progression free (PFS) and overall survival

(OS) compared to Sunitinib. Retrospective analysis and smaller trials have

shown promising results for IO-based therapies also in nccRCC pts.

Methods: SUNIFORECAST is an ongoing, randomized phase-II, multi-

center European trial including pts with advanced or metastatic nccRCC

without prior systemic therapy. Other key inclusion criteria are: avail-

able tumor tissue, Karnofsky >70% and measurable disease per RECIST

1.1. All histological diagnoses are reviewed by a central pathologist. e

study plans to randomize ~306 pts stratied for papillary or non-papil-

lary histology and by the IMDC risk score. Pts will be randomized 1:1 to

either i) Nivolumab 3mg/kg intravenously (IV) plus Ipilimumab 1mg/kg

IVevery 3 weeks for 4 doses followed by Nivolumab xed dose (FD)

240mg IV every 2 weeks (or 480mg IV every 4 weeks) or ii) Standard of

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 101

care according to the approved schedule. Treatment will be discontinued

in case of unacceptable toxicity or withdrawal of informed consent. Pts

may continue treatment beyond progression under certain circumstances.

Primary endpoint is the OS rate at 12 months. Secondary endpoints

include OS rate at 6 and 18 months, median OS, PFS, ORR and quality of

life. e trial is in progress and 260 patients (161 pts with papillary, 96 pts

with non-papillary histology) have been enrolled until now. Clinical trial

identication NCT03075423

Disclosure Statement: e authors declare no conict of interest.

195

The in vitro activity of Cabozantinib as rst- and second-line

agent in metastatic renal cell carcinoma

Angela Zaccagnino1; Bozhena Vynnytska-Myronovska2; Michael Stöckle3;

Kerstin Junker1

1Saarland University, Department of Urology and Pediatric Urology, Homburg,

Deutschland

2University of Saarland, D

3Saarland University, Department of Urology and Pediatric Urology

Background: Cabozantinib (Cbz), a MET/AXL/VEGFR inhibitor, showed

clinical benets as rst and second-line agent in mRCC. We tested the

molecular and cellular eects of Cbz in treatment naïve cells as well as

aer a chronic treatment with Sunitinib (Sun) in vitro.

Methods: e response to Cbz was tested by the IC50 method in the Sun-

resistant cells, 786-O/S and Caki-2/S, and the matching 786-O/WT and

Caki-2/WT. Immune blotting was used to study the signaling pathways.

Result: e 786-O/WT cells showed an IC50 of 10.8µM, while Caki-2/WT

13.6µM. In 786-O/WT, Cbz caused a late onset of the activated receptor

pMET (FC: -2.2) along with, the coupled proteins, Src and STAT3, and

impaired FAK. Under the same settings, pMET was completely inhibited

in Caki-2/WT cells (FC: -10.4). We saw a compensatory activation of FAK

and mTOR marker S6 within 24 h of treatment. As second-line drug, Cbz

had lower ecacy in 786-O/S cells (IC50 of 13µM, p- value 0.02 versus

WT), while no change was observed in Caki-2/S (IC50 of 12.6µM). e

Sun-pretreatment enhanced pMET only in 786-O/S. Following Cbz appli-

cation, the late inhibition of pMET (72 hs) was compensated by the boost

of Src and STAT3 in 786-O/S. In contrast, Cbz impaired pMET thoroughly

in Caki-2/S. In the Sun-pretreated cells, the baseline activation of FAK was

not aected by Cbz. Yet, the Sun-chronic treatment sensitized the resis-

tant cells to the inhibition of mTOR. Finally, the anti-apoptotic protein

Bcl-2 was enhanced at the maximum inhibition of MET, in 786-O/S and

Caki-2/WT.

Discussion: e pMET-driven status in the 786-O/S, Caki-2/WT and

Caki-2/S cells did not sensitize the cells towards Cbz. Aer MET inhi-

bition, the activation of Src-FAK protein axis and Bcl-2 might suggest a

synergy that could weaken Cbz’s antitumor activity.

Conclusion: Our data suggest that pretreatment with Sun could partially

reduce the sensitivity towards Cbz. Still, it was cell line-depended and

thus, it might reect the possible heterogeneity between patients. Overall,

our study provides an understanding of cellular signaling of therapy

sequencing using Cbz in mRCC.

Disclosure Statement: e authors declare no conict of interest.

204

Status and further development of outpatient specialist

medical care in the area of “urological tumors“ (ASV-WE)

Marianne Leitsmann1; Carina Stammann1; Tobias Herrmann1;

Gerald Wilms1; Björn Broge1; Roland Zielke2; Kerstin Bode-Greuel3;

Katja Krug4; Amanda Breckner4; Michel Wensing4; Markus Leibner5;

Clemens Krause5; Hannah Zwiener5; Stefanie Fähndrich5;

Lothar Weißbach6

1aQua - Institut für angewandte Qualitätsförderung und Forschung im

Gesundheitswesen GmbH , Göttingen, Deutschland

2Berufsverband der Deutschen Urologen e.V. (BvDU), Berlin, Deutschland

3Deutsches Institut für Fachärztliche Versorgungsforschung GmbH, Berlin,

Deutschland

4Abteilung für Allgemeinmedizin und Versorgunsgforschung, Medizinische

Fakultät Heidelberg, Heidelberg, Deutschland

5Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik

Deutschland , Berlin, Deutschland

6Gesundheitsforschung für Männer gGmbH, Berlin, Deutschland

Background: Outpatient specialist medical care (ASV) aims to provide

better care for patients with complex diseases through cross-sectoral net-

working and interdisciplinarity care. e study examines the underlying

care processes in the ASV area of urological tumors, focusing on patients

with advanced or metastatic prostate cancer (PCa). We aim to explore

how far the existing ASV meets its expectations regarding innovative,

highly qualied, and sector-connecting care.

Methods: An exploratory and comparative analysis (ASV-care vs. usual

care) is carried out at the level of the structure, process and result qual-

ity met. e methodology follows a “mixed methods” approach. Work

package (WP) 1 comprises the questioning of approx. 1.800 patients. In

WP 2, ASV and non-ASV doctors are surveyed. WP 3 examines cases

of ASV vs. non-ASV patients based on anonymized case data. In WP 4,

interviews and small group discussions are held with ASV doctors, stake-

holder, patient and family representatives. e total results are processed

in workshops and recommendations for action are developed (WP 5). e

project duration is 48 months.

Result: We compiled a suitable patient questionnaire addressing e.g.,

quality of life and coordination of care. As well as a survey tool for urolo-

gists, addressing quality of patient care and intersectoral cooperation. We

further established a framework of criteria to lter for optimal patient care

based on current guidelines and a population-based registry.

Discussion: We will consider whether the results for patients with urolog-

ical tumors, specically advanced or metastatic PCa, can be transferred to

other ASV areas, and at which points the ASV should be further devel-

oped to achieve the specied goals and exploit the potential of optimized

patient care.

Conclusion: Explicit recommendations for action have to be made based

on the knowledge gained for the benet of the patients.

Disclosure Statement: e authors declare no conict of interest. e project is

funded by the Innovation Committee at the Federal Joint Committee under the

funding number 01VSF20026.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts102

222

Real-world study of cabozantinib in patients with advanced

renal cell carcinoma (aRCC) after VEGF-targeted therapy

(CASSIOPE): interim data for patients who had received

prior nivolumab

Paul Hamberg1; Pierre Bigot2; Cristina Suárez3; Philippe Barthelemy4;

Jean-Christophe Eymard5; Cristina Masini6; Pablo Gajate7;

Pascale Dutailly8; Valerie Perrot8; Giuseppe Procopio9

1Franciscus Gasthuis & Vlietland, Rotterdam, Niederlande

2Centre Hospitalier Universitaire d’Angers, Angers, Frankreich

3Hospital Universitari Vall d´Hebron, and Vall d´Hebron Barcelona Hospital

Campus, Vall d´Hebron Institute of Oncology (VHIO), Medical Oncology, Spanien

4Institut de Cancérologie Strasbourg Europe, Strasbourg, Frankreich

5Institut Jean Godinot, Reims, Frankreich

6AUSL-IRCCS di Reggio Emilia, Oncology Unit, Italien

7Hospital Universitario Ramón y Cajal, Madrid, Spanien

8Ipsen, Boulogne-Billancourt, Frankreich

9Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italien

Background: Cabozantinib is a tyrosine kinase inhibitor (TKI) approved

in Europe as monotherapy for aRCC following prior VEGF-targeted

therapy, or for treatment naïve patients with intermediate/poor risk.

We report interim real-world data (RWD) on the use of cabozantinib in

patients with aRCC who have received prior VEGF-targeted therapy and

the checkpoint inhibitor (CPI) nivolumab.1

Methods: CASSIOPE (NCT03419572) is an ongoing, non-interventional

study of cabozantinib in patients with aRCC who have received prior

VEGF-targeted therapy; a pre-planned interim analysis was conducted

when 50% of patients had completed ≥ 3 months of follow-up. is post-

hoc analysis assessed patient characteristics, best overall response (BOR)

based on RECIST 1.1, dose modications and tolerability at 3months in

patients who had also received prior nivolumab.

Result: Of 337 patients included in CASSIOPE, 154 (45.7%) had received

prior nivolumab (median age, 67.5 yrs; 70.8% male, 87.7% clear-cell his-

tology, 96.1% metastatic disease; 80.8% ECOG PS 0–1). Of these patients,

58.4% initiated cabozantinib at 60mg/day; median daily dose during the

study was 40 mg. Overall, 78.6% of patients had dose modications, 66.9%

due to adverse events (AEs) (reduction 46.8% (any) and 43.5% (due to

AEs); interruption, 54.5% and 46.8%; discontinuation, 26.0% and 14.3%).

AEs were reported in 94.8% of patients, most commonly diarrhea (36.4%)

and PPE syndrome (25.3%). During the rst 3months, 58 patients had

an evaluable BOR: 39.7% had partial response, 44.8% stable disease and

12.1% progressive disease (3.4% not evaluable). ere were 17 all-cause

deaths (11.0%).

Discussion: Our ndings are consistent with interim results for the full

CASSIOPE population and contribute valuable RWD on the use of TKIs

aer prior CPI therapy.

Conclusion: is post-hoc analysis of interim CASSIOPE data suggests

that cabozantinib, used in routine care, is broadly tolerable and may

oer tumor response in patients previously treated with VEGF-targeted

therapy and nivolumab.

1Previously presented at ESMO 2021

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

253

Immune-related adverse events can predict progression-free

and overall survival in patients with metastatic renal cell

carcinoma treated with immune checkpoint inhibitors

Matteo Silberg1,2; Laura-Maria Krabbe1; Martin Bögemann1;

Andres Jan Schrader1; Katrin Schlack1

1Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Münster,

Deutschland

2Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum,

Klinik für Urologie, Herne, Deutschland

Background: Dierent combination therapies with anti-PD-1/PD-L1- or

-CTLA4 immune checkpoint inhibition (ICI) are widely used in patients

(pts) with metastatic renal cell carcinoma (mRCC). Biomarkers or clinical

characteristics predicting response to treatment are rare.

Methods: In our retrospective cohort study, we analyzed data based on

digital charts of 134 pts with mRCC receiving ICI (Nivolumab, Ipilimumab

and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib)

between 2015 and 2020 at the Department of Urology, University Hospital

Muenster. To identify predictors of overall- (OS) and progression-free

survival (PFS), with a special focus on the presence of immune-related

adverse events (irAE), we used Cox regression and Kaplan-Meier-analysis.

Result: Median age was 66 years (IQR 28-85). We observed irAE in 85 pts

(63.4%). Cutaneous events were most common (38.8%) followed by endo-

crine (24.6%) and hepatic (14.2%) irAE. 49 pts (36.6%) required cortico-

steroid therapy due to irAE. In multivariate analysis the presence of irAE

(HR 0.46, P=0.008) was associated with prolonged PFS. Platelets increase

under ICI (HR 2.29, P=0.018) and lymph node metastasis (HR 1.98,

P=0.037) were associated with worse PFS. Considering OS, occurrence of

irAE (HR 0.28, P=0.002), ECOG status (HR 2.13, P=0.048), IMDC score

(HR 2.74, P=0.018) and LDH (HR 4.65, P<0.001) remained independent

predictors. In Kaplan-Meier-analysis the median PFS was signicantly

improved for the irAE subgroup (15 months) compared to in the non-

irAE subgroup (5 months, P<0.001). Median OS was not reached in the

irAE subgroup. Nevertheless, there was a signicant improvement for pts

with irAE compared to the non-irAE subgroup (25 months, P=0.002).

Corticosteroid therapy did not aect survival outcome.

Discussion & Conclusion: e presence of irAE under therapy with ICI

in pts with mRCC is associated with better PFS and OS. erefore, irAE

should be treated consequently and a permanent discontinuation of ICI

should not be decided prematurely.

Disclosure Statement: No conict of interest.

266

Interim data of eectiveness and safety of nivolumab plus

ipilimumab combination therapy (NIVO+IPI) in rst line (1L)

advanced/metastatic renal cell carcinoma (aRCC) from the

German non-interventional study (NIS) NORA

Jens Bedke1; Harald Müller-Huesmann2; Hanjo Belz3; Eyck von der Heyde4;

Martin Bögemann5; Arne Strauß6; Philipp Ivanyi7; Jörg Wiegand8;

Andrea Autengruber9; Marc-Oliver Grimm10; Viktor Grünwald11

1Universitätsklinikum Tübingen, Tübingen, Deutschland

2Brüderkrankenhaus St. Josef, Paderborn, Deutschland

3Zeisigwaldkliniken Bethanien Chemnitz, Chemnitz, Deutschland

4Onkologische Praxis am Raschplatz, Hannover, Deutschland

5Universitätsklinikum Münster, Münster, Deutschland

6Universitätsmedizin Göttingen, Georg-August-Universität Göttingen,

Göttingen, Deutschland

7Medizinische Hochschule Hannover, Hannover, Deutschland

8Gemeinschaftspraxis für Hämatologie & Onkologie am St. Josef Krankenhaus,

Moers, Deutschland

9Bristol Myers Squibb, München, Deutschland

10Universitätsklinikum Jena, Jena, Deutschland

11Universitätsklinikum Essen, Westdeutsches Tumorzentrum Essen, Essen,

Deutschland

Background: e CheckMate 214 phase 3 trial demonstrated a sustained

survival benet in 1L patients (pts) with intermediate/poor-risk aRCC for

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 103

NIVO+IPI versus sunitinib. Here, we report real-world data on eective-

ness and safety for 1L NIVO+IPI as an interim analysis of the German NIS

NORA (NCT02940639).

Methods: Adults with aRCC and 1L NIVO+IPI treatment (tx) according

to the label were eligible. e primary study objective is overall survival

(OS) over a 5-yr follow-up period. is interim analysis (database cut

Jan 31 2022) reported data on demographics, disease characteristics and

safety using descriptive statistics. Kaplan-Meier methodology was used

to estimate progression free survival (PFS, investigator assessed or per

RECIST) and OS.

Result: A total of 258 pts (78.7 % with clear cell RCC) were enrolled from

Jan 2019 - Dec 2021. Most patients (71.7%) were male and mean age was

65.8 yrs (age groups: < 65 yrs, 46.1%; ≥ 65 to < 75 yrs, 31.0%; ≥ 75 yrs,

22.9%). According to International Metastatic RCC Database Consortium

(IMDC) score, 69% had intermediate, and 26% had poor risk RCC with

proportional distribution among age groups; pts with Karnofsky score < 80

was 17.1% and a higher fraction of pts with Karnofsky score < 80 (34.1%)

was detected in elderly (≥ 75 yrs). 62.8 % of pts had prior nephrectomy.

Median follow-up was 6.3 mo, and median duration of treatment was 6.3

mo; 105 pts were still on tx, while 153 pts discontinued tx. Median PFS

was 6.6 mo (95% CI, 4.9-9.1 mo) and OS probability at 12 months was

66.1%. At least one treatment-related AE (trAE)/serious trAE of any grade

was reported in 55.8%/18.6% of pts.

Discussion & Conclusion: ese rst results on 1L NIVO+IPI in routine

care with a limited median follow-up period provides supporting infor-

mation on eectiveness and safety of NIVO+IPI in aRCC. Our real-world

patient cohort diered regarding pts characteristics when compared to

CheckMate 214, and no new safety signals were detected.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

300

Surgical management of localised renal cell carcinoma in

Hessian hospitals - a population-based analysis

Katharina Bernhardt1; Petra Neuser1; Soo-Zin Kim-Wanner1

1Hessisches Krebsregister, Hessisches Landesprüfungs- und Untersuchungsamt

im Gesundheitswesen, Landesauswertungsstelle, Frankfurt, Deutschland

Background: During the past decade, the treatment paradigm for localised

renal cell carcinomas (RCC) has shied towards nephron-sparing surgery

as oncologic outcomes have shown to be equivalent to radical nephrec-

tomy and towards minimally invasive surgery with reduced intraoperative

blood loss and shorter convalescence. To date, little data are available on

the implementation of laparoscopy in partial and radical nephrectomy in

Germany. e purpose of this study was to analyse the surgical manage-

ment of localised RCC and compare the rates of organ-saving and mini-

mally invasive resections among dierent care providers.

Methods: Data of patients with RCC diagnosed between 2015-2019 were

extracted from the database of the Hessian cancer registry. 2014 patients

with age ≥ 18 years and ICD-10 C64 were included in the analysis.

Result: 1320 of 2014 RCC were reported by 24 care providers with a UICC

stage I: 58% and II: 8%. 87% received surgical treatment. e 30-day mor-

tality aer resection was 2% and T1-2 tumours were completely excised

(R0) in 93% of the patients. Nephron-sparing surgery was observed in

67% of pT1 cases, but varied among hospitals (range: 44-79%) with a

higher rate of 72% in two high volume centres with ≥ 50 resections annu-

ally. T1 tumours were excised minimally invasive in 14% of the cases

(high volume centres: 14% and 36%) and 50% of the medical institutions

exclusively performed open surgical resections in localised RCC. Among

laparoscopically removed T1 tumours, 56% were partially and 44% were

radically resected.

Discussion: So far, comprehensive implementation of nephron-spar-

ing resections and especially minimally invasive surgery have not been

achieved. High disparities among Hessian hospitals were detected.

Nevertheless, the low 30-day mortality and high R0 rate indicated an over-

all high quality of surgical excisions.

Conclusion: More eorts have to be made for a widespread and con-

sistent implementation of the recommended therapy for localised RCC

to improve the quality of surgical treatment and reduce morbidities in

patients.

Disclosure Statement: e authors declare no conict of interest.

308

Analysis of the CLEAR study in patients (pts) with advanced

renal cell carcinoma (RCC): depth of response and ecacy for

selected subgroups in the lenvatinib (L) + pembrolizumab (P)

and sunitinib (S) treatment arms

Viktor Grünwald1; Thomas Powles2; Evgeny Kopyltsov3; Vadim Kozlov4;

Teresa Alonso Gordoa5; Masatoshi Eto6; Thomas Hutson7; Robert Motzer8;

Eric Winquist9; Pablo Maroto10; Bhumsuk Keam11; Giuseppe Procopio12;

Shirley Wong13; Bohuslav Melichar14; Frederic Rolland15; Mototsugu Oya16;

Karla Rodriguez-Lopez17; Kenichi Saito18; Alan Smith19; Camillo Porta20

1University Hospital Essen, Essen, Deutschland

2The Royal Free NHS Trust, London, England, Vereinigtes Königreich

3State Institution of Healthcare “Regional Clinical Oncology Dispensary”, Omsk,

Russische Föderation

4State Budgetary Health Care Institution “Novosibirsk Regional Clinical Oncology

Dispensary”, Novosibirsk, Russische Föderation

5Hospital Universitario Ramón y Cajal, Madrid, Spanien

6Kyushu University, Fukuoka, Japan

7Texas Oncology, Dallas, TX, USA

8Memorial Sloan Kettering Cancer Center, New York, NY, USA

9Western University, London, Ontario, Kanada

10Hospital de la Santa Creu i Sant Pau, Barcelona, Spanien

11Seoul National University Hospital, Seoul, Republik Korea

12Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italien

13Western Health, VIC, Australien

14Palacký University Medical School and Teaching Hospital, Olomouc,

Tschechische Republik

15Centre René Gauducheau Centre de Lutte Contre Le Cancer Nantes, Saint-

Herblain, Frankreich

16Keio University School of Medicine, Tokyo, Japan

17Merck & Co., Inc., Kenilworth, NJ, USA

18Eisai Inc., Woodcli Lake, NJ, USA

19Eisai Ltd., Hateld, England, Vereinigtes Königreich

20San Matteo University Hospital Foundation, Pavia, Italien

Background: In the phase 3 CLEAR study, L+P had signicant PFS and

OS benets, and improved ORR vs S in 1L advanced RCC.

Methods: Pts were randomized 1:1:1 to 1 of 3 treatment arms: L 20 mg

PO QD + P 200 mg IV Q3W; L 18 mg + everolimus 5 mg PO QD; or S

50 mg PO QD (4 wks on/2 wks o). We report PFS, OS, and ORR based

on IMDC risk group (favorable and intermediate/poor) and target kidney

lesion presence at baseline (post hoc analysis). Post hoc 6-mo landmark

analyses assessed the association between tumor shrinkage and OS. Pts

who were alive at 6 mos were grouped based on maximum tumor shrink-

age from baseline or conrmed complete response (CR) up to 6 mos.

Tumor assessments were performed by independent review committee

per RECIST v1.1.

Result: Among 1069 pts, 355 were assigned to L+P and 357 to S. Median

follow-up was 27 mos for L+P and 26 mos for S. L+P was favored vs S in

the IMDC-intermediate/poor subgroup (n=243 vs 229) for PFS (median

22.1 vs 5.9 mos, HR 0.36, 95% CI 0.28-0.47), OS (HR 0.58, 95% CI 0.42-

0.80), and ORR (72.4% vs 28.8%, odds ratio [OR] 6.60, 95% CI 4.39-

9.90) as well as in the IMDC-favorable subgroup (n=110 vs 124) for PFS

(median 28.1 vs 12.9 mos, HR 0.41, 95% CI 0.28-0.62) and ORR (68.2%

vs 50.8%, OR 2.00, 95% CI 1.17-3.42), with too few OS events to evaluate.

In pts with target kidney lesions, median PFS (22.1 vs 7.5 mos, HR 0.40,

95% CI 0.25-0.65), median OS (not reached vs 30.7 mos, HR 0.44, 95% CI

0.26-0.77), and ORR (71.8% vs 27.0%, OR 10.55, 95% CI 4.54-24.52) were

improved with L+P vs S (n=78 vs 74). In the 6-mo landmark analysis in

the L+P arm, 24 mo OS rate was 100% (95% CI not estimable [NE]-NE)

for pts with conrmed CR, and 91.7% (95% CI 53.9-98.8) both for pts

with >75% to <100%, and 100% target-lesion reduction.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts104

Discussion: In pts with target kidney lesions and across evaluable IMDC

subgroups, L+P conferred survival benets vs S similar to benets

observed in the overall population.

Conclusion: L+P improved PFS, OS, and ORR vs S in pts with target kid-

ney lesions and across evaluable IMDC risk groups. Overall, pts treated

with L+P who had >75% reduction in target lesions had similar OS rates

to pts with CR.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

326

Ecacy and safety of darolutamide in patients with

nonmetastatic castration-resistant prostate cancer (nmCRPC)

and a prostate-specic antigen doubling time (PSADT) > and

≤ 6 months

Martin Schostak1; Martin Bögemann2; Matthew R. Smith3; Neal D. Shore4;

Teuvo L.J. Tammela5; Albertas Ulys6; Egils Vjaters7; Sergey Polyakov8;

Mindaugas Jievaltas9; Murilo Luz10; Boris Alekseev11; Iris Kuss12;

Marie-Aude Le Berre13; Amir Snapir14; Toni Sarapohja14; Karim Fizazi15

1Department of Urology, Magdeburg University Medical Center, Magdeburg,

Deutschland

2Department of Urology, Münster University Medical Center, Münster,

Deutschland

3Massachusetts General Hospital Cancer Center and Harvard Medical School,

Urologic Oncology, Boston, MA, USA

4Carolina Urologic Research Center , Atlantic Urology Clinics, Myrtle Beach,

SC,USA

5Tampere University Hospital, Tampere, USA

6Institute of Oncology, Vilnius University, Vilnius, Lithuania

7Pauls Stradins Clinical University Hospital, Department Of Urology, Riga, Latvia

8N.N. Alexandrov National Cancer Centre, Department of Urology, Minsk, Belarus

9Lithuanian University of Health Sciences, Medical Academy, Department of

Urology, Kaunas, Lithuania

10Hospital Erasto Gaertner, Curitiba, Brasilien

11Hertzen Moscow Oncology Research Institute, Moscow, Russische Föderation

12Bayer AG, Berlin, Deutschland

13Bayer Healthcare, Loos, Frankreich

14Orion Corporation Orion Pharma, Espoo, Finnland

15Institut Gustave Roussy, University of Paris-Sud, Villejuif, Frankreich

Background: In the phase 3 ARAMIS trial, darolutamide (DARO) signi-

cantly improved metastasis-free survival (MFS) and Overall survival (OS)

in patients with nmCRPC and PSADT ≤10 months. Patients in ARAMIS

were stratied by PSADT ≤6 months and >6 months. Here we present

the ecacy and safety of DARO in ARAMIS participants in subgroups

by PSADT.

Methods: e double-blind, placebo-controlled phase III ARAMIS trial

randomized 1509 patients in a 2:1 ratio to receive DARO 600 mg BID

(n=955) or placebo (PBO; n=554), while continuing androgen depri-

vation therapy. Patients were stratied by PSADT (≤6 or >6 months) to

assess the eect on ecacy and safety.

Result: In the overall population, median (range) baseline PSADT was

4.4 (0.7–11.0) months in the DARO arm and 4.7 (0.7–13.0) months in the

PBO arm. Around 30% of patients in each arm had PSADT >6 months.

In the subgroup of patients with PSADT >6 months, the risk of metastasis

or death was reduced by 62% with DARO as compared with PBO (hazard

ratio [HR] 0.38; 95% condence interval [CI] 0.26–0.55), in line with both

the overall population (HR 0.41; 95% CI 0.34–0.50) and with patients

with PSADT ≤6 months (HR 0.41; 95% CI 0.33–0.52). Median (95% CI)

MFS was not estimable (40.5 months–not estimable) and 34.3 months

(30.8 months–not estimable) for patients with PSADT >6 months and

≤6 months, respectively. At nal analysis, Overall survival was improved

in both subgroups in line with overall population. e safety prole of

DARO, including AEs of interest, for patients with PSADT >6 months was

consistent with that of the overall study population.

Conclusion: e MFS benet and safety of DARO is similar in the sub-

set of patients with PSADT >6 months and the overall ARAMIS study

population

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

327

Time Course Prole of Adverse Events of Interest and Serious

Adverse Events With Darolutamide in the ARAMIS Trial

Markus Grabbert1; Christian Gratzke1; Karim Fizazi2; Neal Shore3;

Matthew Smith4; Susan Feyerabend5; Joan Carles6; Thierry Lebret7;

Egils Vjaters8; Patrick Werbrouck9; Marina Miskic10; Anja Schmall11;

Marie Aude Le Berre12; Gustavo Borghesi13; Frank Verholen14

1University Hospital Freiburg, Freiburg, Deutschland

2Institut Gustave Roussy, University of Paris Saclay, Villejuif, Frankreich

3Carolina Urologic Research Center, Myrtle Beach, SC, USA

4Massachusetts General Hospital, Boston, MA, USA

5Studienpraxis Urologie, Nuertingen, Deutschland

6Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron,

Barcelona, Spanien

7Hopital Foch, Suresnes, Frankreich

8P. Stradins Clinical University Hospital, Riga, Latvia

9AZ Groeninge, Kortrijk, Belgien

10Bayer Consumer Care AG, Basel, Schweiz

11Bayer Vital GmbH, Leverkusen, Deutschland

12Bayer Healthcare SAS, Loos, Frankreich

13Bayer AG, Berlin, Deutschland

14Bayer Healthcare SAS, Basel, Schweiz

Background: Men with nonmetastatic castration-resistant prostate cancer

(nmCRPC) are generally asymptomatic and may receive prolonged treat-

ment with androgen receptor inhibitors. Understanding the burden and

time course of adverse events (AEs) commonly associated with ARIs that

may impact patients’ daily life will help inform optimal treatment selec-

tion. We present analyses of time to AEs of interest (fatigue, falls, fracture,

hypertension, mental impairment, rash) and the cumulative incidence of

these AEs, grade 3/4 AEs, and serious AEs from the ARAMIS trial.

Methods: Men with nmCRPC were randomized 2:1 to darolutamide

(DARO; n=955) or placebo (PBO; n=554) while continuing androgen

deprivation therapy. e cumulative incidence of AEs was analyzed using

Kaplan-Meier estimates for the rst 24 months (mo) of the double-blind

(DB) period to ensure >10% of the population in each treatment cohort.

Time interval–specic analysis determined new event rates at each sched-

uled study visit.

Result: e overall incidence of AEs of interest in the DARO group was

low and ≤2% dierent from that in the PBO group, except for fatigue.

During the rst month of DARO and PBO treatment, new event rates

were very low and similar for falls (0.2%, 0.7%), fractures (0.4%, 0.5%),

mental impairment (0%, 0.4%), hypertension (1.7%, 1.1%), and rash

(0.7%, 0.2%). In men who had fatigue during the rst 24 mo (12.6%,

8.3%), almost half of the men experienced fatigue onset during the rst

month in both arms (5.9%, 4.0%). e cumulative incidence of rash was

2.9% (PBO 1.1%) at 24 mo, with half of the events occurring in the rst 4

mo and almost all being grade 1 or 2. e rate of initial onset and cumu-

lative incidence of grade 3/4 AEs and serious AEs were similar for DARO

and PBO groups over 24 months.

Conclusion: e time course prole of most AEs of interest, grade 3/4

AEs, and serious AEs conrms the safety prole of DARO, showing a sim-

ilar onset and cumulative incidence versus PBO. Most events of fatigue

were reported early in treatment, and the incidence of rash was very low,

with almost all being grade 1 or 2 events.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 105

328

Clinical benet and safety prole of darolutamide in

patients who crossed over to darolutamide from placebo

during the open-label period of the phase 3 ARAMIS study

Tilman Todenhöfer1; Susan Feyerabend1; Neal Shore2; Matthew Smith3;

Evgeny Kopyltsov4; Igor Antonyan5; Jan-Erik Damber6;

Donatello Gasparro7; Asif Yildirim8; Egils Vjaters9; Jorge Ortiz10;

Shankar Srinivasan10; Toni Sarapohja11; Karim Fizazi12

1Studienpraxis Urologie, Nuertingen, Deutschland

2Carolina Urologic Research Center, Myrtle Beach, SC, USA

3Massachusetts General Hospital, Boston, MA, USA

4BHI of Omsk Region Clinical Oncological Dispensary, Omsk, Russische

Föderation

5Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine

6University of Gothenburg, Gothenburg, Schweden

7Azienda Ospedaliero-Universitaria di Parma, Parma, Italien

8Istanbul Medeniyet University Goztepe Training And Research Hospital,

Istanbul, Türkei

9P. Stradins Clinical University Hospital, Riga, Latvia

10Bayer Healthcare, Whippany, NJ, USA

11Orion Corporation Orion Pharma, Espoo, Finnland

12Institut Gustave Roussy, University of Paris Saclay, Villejuif, Frankreich

Background: Darolutamide (DARO) signicantly prolonged metasta-

sis-free survival (MFS) and overall survival (OS) vs placebo (PBO) in

men with nonmetastatic castration-resistant prostate cancer in ARAMIS.

DARO has a favorable safety prole, showing ≤2% dierence between

DARO and PBO for most adverse events (AEs) of interest associated with

androgen receptor inhibitors. Fatigue was the only AE with >10% inci-

dence in the DARO arm (13.2% vs 8.3% in PBO arm). Aer unblinding of

ARAMIS,170 patients (pts) receiving PBO crossed over (CO) to open-la-

bel (OL) DARO. Here, we present clinical benet and safety in CO pts.

Methods: Pts with nmCRPC and prostate-specic antigen (PSA) dou-

bling time ≤10 months were randomized 2:1 to DARO (n=955) or PBO

(n=554) while continuing androgen deprivation therapy. For PBO to

DARO CO pts at nal analysis, PSA outcomes were used to assess clinical

benet because the treatment duration was not long enough to assess MFS

or OS. e last outcome measurement before CO from PBO to DARO was

the CO baseline value. AEs during the double-blind (DB) and OL periods

were compared with the CO period for the same observation time, consis-

tent with the median treatment duration in CO pts.

Result: PBO to DARO CO pts had higher median PSA values (19.80 vs

7.06 ng/mL) and poorer Eastern Cooperative Oncology Group perfor-

mance status (ECOG ≥1 in 31% vs 25%) at the start of DARO treatment

compared with study entry. Median treatment duration for CO pts was 11

months. At any time aer CO, 85% of CO pts had a PSA50 response. At

16 weeks aer CO, 51% had PSA90 response. Compared with the DARO

DB period during 11 months of treatment, DARO CO pts had similar or

lower rates of any AEs (75.8% vs 70.0%), serious AEs (14.8% vs 15.3%),

and AEs leading to study drug discontinuation (5.9% vs 4.7%). Most AEs

of interest had a lower incidence in CO pts compared with the DB period.

Conclusion: Although the OS and MFS results substantiate the clear

benet of early treatment with DARO, there were consistent safety and

potential clinical benets for pts who received DARO following CO from

PBO in ARAMIS.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

390

Trends in rst-line treatment of early stage prostate cancer

with data from the Cancer Registry of Baden-Württemberg

(Germany)

Tilo Vogel1; Irina Surovtsova1; Franziska Kanz1; Bettina Balzer1;

Philipp Morakis1

1Klinische Landesregisterstelle, Krebsregister Baden-Württemberg, Stuttgart,

Deutschland

Introduction: Treatment options for early stage prostate cancer include

radical and ablative surgery, denitive radiotherapy and active sur-

veillance/ wait and see. Further, Androgen-deprivation may be used as

palliative systemic therapy. Management is guided by life expectance,

comorbidities, risk and patients preferences. e present population

based study uses data from the Cancer Registry of Baden-Württemberg

(BW) to examine trends in the management of early stage disease.

Objective: Aim of this study was to show trends in the primary treatment

modality of early stage incidence prostate cancer.

Patients and Methods: Patients with incident prostate adenocarcinoma

diagnosed between 2013 until 2019 and reported to the Cancer Registry

were included. Primary therapy modalities (surgery, radiotherapy, wait

and see/ active surveillance and systemic therapy) of early stage T1/T2

disease were analysed. Radical and ablative surgery procedures were iden-

tied based on the operation and procedure code reported to the Registry.

e frequency of each treatment modality for each year was calculated for

low, intermediate and high risk groups according to the D´Amico classi-

cation for a total number of about 10.000 patients.

Results: In this analysis, radical surgery was the most frequently applied

primary therapy (> 60%) for early stage prostate adenocarcinoma for all

risk groups. For the intermediate risk group, a slight increase in the use of

radical surgery was observed from 2013 to 2019, while systemic therapy

was less used over the years. e use of radiotherapy, the second mostly

used primary treatment, and conservative management (wait and see /

active surveillance) did not change substantially.Ablative procedures were

used with low rate and predominantly applied in the low risk group.

Conclusion: Despite radical surgery procedures for prostate cancer poses

severe side eects, data of the Cancer Registry showed their preferential

use in early stage prostate cancer for all risk groups during the years 2013

to 2019 and a trend to their increased use in the intermediate risk group.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts106

507

Clinical and molecular characterization of patients (pts)

with Neuroendocrine Prostate Cancer (NEPC) treated at a high

volume cancer center

Ray Maria Vittoria Stiens1; Saskia Ting2; Henning Reis3; Tibor Szarvas4;

Lukas Püllen4; Thomas Hilser1; Lara Helena Sichward2; Boris Hadaschik4;

Kurt Werner Schmid5; Hans-Ulrich Schildhaus6; Martin Schuler7;

Viktor Grünwald8; Isabel Virchow1

1Medical Faculty University Duisburg-Essen, West German Cancer Center,

Department of Medical Oncology, Essen, Deutschland

2Medical Faculty University Duisburg-Essen, West German Cancer Center,

Institute of Pathology, Essen, Deutschland

3University Hospital Frankfurt, Johann Wolfgang Goethe University, Institute of

Pathology, Deutschland

4Medical Faculty University Duisburg-Essen, West German Cancer Center,

Department of Urology, Essen, Deutschland

5Medical Faculty University Duisburg-Essen, West German Cancer Center,

Institute of Pathology, German Cancer Consortium (DKTK), Essen, Deutschland

6Medical Faculty University Duisburg-Essen, West German Cancer Center,

Institute of Pathology, German Cancer Consortium (DKTK), Essen,

7Medical Faculty University Duisburg-Essen, West German Cancer Center,

Department of Medical Oncology, German Cancer Consortium (DKTK), Essen,

Deutschland

8Medical Faculty University Duisburg-Essen, West German Cancer Center,

Department of Medical Oncology, Department of Urology, Essen, Deutschland

Background: Primary NEPC (p-NEPC) is a rare disease (<1%)

whereastreatment emergent (t-NEPC) can be found in 30% of metastatic

castration-resistant tumors. Reported overall survival (OS) is poor with

16 months (mo). Mechanisms accounting for resistance and response to

chemotherapy (CTX), androgen deprivation (ADT) or neuroendocrine

transdierentiation are still not understood. Here, we present rst clin-

icopathological data of a metastatic NEPC cohort, treated at the West

German Cancer Center Essen (WTZ).

Methods: Clinical and epidemiological data of NEPC patients diagnosed

between 1998 and 2021 were retrospectively retrieved from the institu-

tional database. Clinicopathological characteristics and overall survival

(OS) were investigated. Standard immunohistochemistry and extensive

mutational analyses using next generation sequencing (NGS) were per-

formed exploratory on 66 genes.

Result: 25 pts with NEPC were identied; 14 pts were classied as p-NEPC,

11 as t-NEPC. Median age was 66.2 years. Median PSA was 38.5 ng/ml.

As rst-line treatment 7 pts received palliative platinum- or taxane-based

CTX, 15 pts received an ADT and 3 pts were irradiated. Median OS was

18 mo. For 14 pts sucient surplus tissue samples could be retrieved and

validated. For 3 representative cases an exploratory NGS analysis was per-

formed. 1 pt showed no alteration, 1 pt showed a somatic BRCA1 Exon

10 mutation considered likely benign/of unknown signicance (VUS), 1

pt showed a pathogenic BRCA2 Exon10 mutation and simultaneously a

RNF43 Exon 9 mutation.

Discussion: BRCA1/2 mutations were found in 2 samples of p-NPEC

whereas the t-NEPC sample showed no alterations. e pt revealing a

pathogenic BRCA2 mutation and a concurrent mutation in RNF43 has an

extraordinary OS of 6.2 years and was alive at the last follow-up.

Conclusion: Outcome of this real-world NEPC patient cohort compares

favorably with published data. Our exploratory ndings support the

implementation of BRCA1/2 mutation testing in this patient population.

Disclosure Statement: e authors declare no conict of interest.

591

PSMA-PET- and mpMRI-guided focal dose escalated

radiotherapy in primary prostate cancer patients – a planned

safety analysis of a two-armed prospective phase II trial

(HypoFocal)

Simon K.B. Spohn1,2,3; Mark Gainey4; Marius Kamps5; Christian Gratzke5;

Michael MIX6; Juri Ruf6; Matthias Benndorf7; Sebastian Zschaeck8;

Pirus Ghadjar8; Dimos Baltas1,4; Anca-L. Grosu1,3; Constantinoos

Zamboglou1,2,3,9

1German Cancer Consortium (DKTK), Partner Site Freiburg, Deutschland

2Faculty of Medicine - University of Freiburg, Berta-Ottenstein-Programme,

Deutschland

3University Medical Center, Department of Radiation Oncology, Freiburg,

Deutschland

4University Medical Center, Division of Medical Physics - Department of

Radiation Oncology, Freiburg, Deutschland

5University Medical Center, Department of Urology, Freiburg, Deutschland

6University Medical Center, Department of Nuclear Medicine, Freiburg,

Deutschland

7University Medical Center, Department of Radiology, Freiburg, Deutschland

8Charité – Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology,

Berlin, Deutschland

9European University of Cyprus, German Oncology Center, Limassol, Zypern

Background: Due to superior intraprostatic tumour mass (ITM) cover-

age focal dose escalated radiotherapy (RT) to multiparametric magnet

resonance tomography- (mpMRI) and positron emission tomography

targeting prostate specic membrane antigen- (PSMA-PET) dened

boost volumes might improve treatment of primary prostate cancer (PCa)

patients. e non-randomized HypoFocal phase II trial investigates the

implementation of PSMA-PET in focal therapy planning. We present the

planned safety analysis aer 6 months of follow-up (FU).

Methods: Intermediate- and high-risk PCa patients with cN0 and cM0 in

mpMRI and PSMA-PET were included. Arm A was treated with 60 Gy in

20 fractions with boost up to 75 Gy to mpMRI- and PSMA-PET-dened

ITMs. Arm B was treated with single fraction high-dose-rate brachyther-

apy (HDR-BT) with 15 Gy to the prostate and boost up to 19 Gy to the

ITMs, followed by RT with 44 Gy in 20 fractions. We assessed gastro-

intestinal (GI) and genitourinary (GU) toxicities according to CTCAE

v5.0, IPSS score and quality of life (QoL) with EORTC questionnaires

QLQ-PR25 and QLQ-PR30.

Result: 25 patients were enrolled in each arm in two centers (Freiburg and

Berlin). Median boost volumes were 10.2 ml in arm A and 6.8 ml in arm B.

Median mean dose to the boost volume was 70 Gy in arm A and median

D90 to was 19 Gy in arm B. Cumulative grade 2 GU and GI toxicities were

36% and 16% in arm A and 48% and 12% in arm B. No grade 3 toxicity

was observed at 6 months FU. Toxicities, IPSS and QoL-scores were not

statistically signicantly dierent between baselines and 6 months of FU.

Two grade 3 GI toxicities were observed 9 and 12 FU, related to biopsy

Discussion: Combined PSMA-PET and mpMRI-based boost denition

results in signicantly larger volumes and focal dose escalation was feasi-

ble with acceptable acute toxicities without compromising QoL.

Conclusion: Implementation of PSMA-PET for focal therapy planning

should be investigated in larger cohorts. Radiation proctitis demands

careful management.

Disclosure Statement: e authors declare no conict of interest. Abstract was

submitted to EMUC2021.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 107

780

Symptomatic vs. asymptomatic renal cell carcinoma

in Germany: 39-months follow-up data from the non-

interventional, prospective VERSUS study by d-uo

Manfred Johannsen1; Rolf Harald Eichenauer2; Jörg Klier3; Frank König1;

Robert Schönfelder2; Jörg Schröder1; Elke Hempel1; Christian Doehn4

1Berlin, Berlin, Deutschland

2Hamburg, Hamburg, Deutschland

3Köln, Köln, Deutschland

4Lübeck, Lübeck, Deutschland

Background: In May 2018, the German Uro-Oncologists (Deutsche

Uro-Onkologen, d-uo) opened their prospective VERSUS study

(VERSorgUngsStudie, VERSUS) for the documentation of outpatient

diagnosis and treatment of urological tumors. is analysis addressed

the question whether age and tumor stage at diagnosis diered between

symptomatic vs. asymptomatic renal cell carcinoma (RCC) cases.

Methods: VERSUS is a nation-wide non-interventional, prospective,

multicentric study for the documentation and evaluation of outpatient

diagnosis, treatment and follow-up of urological tumors using descrip-

tive statistics. In this analysis we evaluated patients with rst diagnosis of

RCC. In the d-uo database, the cause of rst diagnosis (e.g. early detec-

tion) can be documented.

Result: Up to August 2021, 10.0799 patients with rst diagnosis of a uro-

logical tumor were documented. Out of these, 790 patients (7.8%) had

RCC. 70.5% were men and 29.5% were women, median age was 70.0 years

(men 69.9, women 70.1). In 230 cases (32.8%, median age 68.6 years),

RCC was diagnosed because of symptoms. Patients wih symptoms had

UICC stage I and IV in 49.4% and 16.3%, respectively. In contrast, asymp-

tomatic patients had UICC stage I and IV in 73.2% and 2.4%, respectively.

Discussion: Patients with symptomatic RCC are younger and display

more unfavourable tumor stages at diagnosis.

Conclusion: e VERSUS study continues to collect epidemiologic and

clinical data of patients with RCC.

Disclosure Statement: e authors declare no conict of interest.

794

Early detected vs. non-early detected prostate cancer

in Germany: 39-months follow-up data from the

non-interventional, prospective VERSUS study by d-uo

Frank König1; Rolf Harald Eichenauer2; Jörg Klier3; Manfred Johannsen1;

Robert Schönfelder2; Jörg Schröder1; Elke Hempel1; Christian Doehn4

1Berlin, Berlin, Deutschland

2Hamburg, Hamburg, Deutschland

3Köln, Köln, Deutschland

4Lübeck, Lübeck, Deutschland

Background: In May 2018, the German Uro-Oncologists (Deutsche

Uro-Onkologen, d-uo) opened their prospective VERSUS study

(VERSorgUngsStudie, VERSUS) for the documentation of outpatient

diagnosis and treatment of urological tumors. is analysis addressed the

question whether age and tumor stage at diagnosis diered between early

detected vs. non-early detected prostate cancer (PCa) cases.

Methods: VERSUS is a nation-wide non-interventional, prospective,

multicentric study for the documentation and evaluation of outpatient

diagnosis, treatment and follow-up of urological tumors using descriptive

statistics. In this analysis we evaluated patients with rst diagnosis of PCa.

In the d-uo database, the cause of rst diagnosis (e.g. early detection) can

be documented.

Result: Up to August 2021, 10.079 patients with rst diagnosis of a uro-

logical tumor were documented. Out of these, 6.291 patients (62.4%) had

PCa. In 3000 cases (47.7%), PCa was diagnosed following early detection

vs. 3.291 cases (52,3%) without early detection.

Median age of patients with early-detected vs. non-early detected PCa

was 73.3 vs. 76.7 years, respectively. TNM- -stages were available in 4.456

(70.8%) patients. Patients with early-detected PCa had stage T1 and M1 in

59.8% and 2.9% while patients with non-early detected PCa had stage T1

and M1 in 56.7% and 7%.

Discussion: Patients with early-detected PCa were younger and had

more favourable tumor stages at rst diagnosis than those with non-early

detected PCa.

Conclusion: e VERSUS study continues to collect epidemiologic and

clinical data of patients with PCa.

Disclosure Statement: e authors declare no conict of interest.

795

Symptomatic vs. asymptomatic urothelial carcinoma in Germany:

39-months follow-up data from the non-interventional;

prospective VERSUS study by d-uo

Rolf Harald Eichenauer1; Manfred Johannsen2; Jörg Klier3; Frank König2;

Robert Schönfelder1; Jörg Schröder2; Elke Hempel2; Christian Doehn4

1Hamburg, Hamburg, Deutschland

2Berlin, Berlin, Deutschland

3Köln, Köln, Deutschland

4Lübeck, Lübeck, Deutschland

Background: In May 2018, the German Uro-Oncologists (Deutsche

Uro-Onkologen, d-uo) opened their prospective VERSUS study

(VERSorgUngsStudie, VERSUS) for the documentation of outpatient

diagnosis and treatment of urological tumors. is analysis addressed

the question whether age and tumor stage at diagnosis diered between

symptomatic vs. asymptomatic urothelial carcinoma (UC) cases.

Methods: VERSUS is a nation-wide non-interventional, prospective,

multicentric study for the documentation and evaluation of outpatient

diagnosis, treatment and follow-up of urological tumors using descriptive

statistics. In this analysis we evaluated patients with rst diagnosis of UC.

In the d-uo database, the cause of rst diagnosis (e.g. early detection) can

be documented.

Result: Up to August 2021, 10.079 patients with rst diagnosis of a uro-

logical tumor were documented. Out of these, 2.533 patients (25.1%)

had UC. 77.5% were men and 22.5% were women, median age was 75.2

years (men 75.3, women 74.3). In 1.404 cases (55.4%), UC was diagnosed

because of symptoms vs. 1.129 cases (44.6%) without symptoms. Patients

with symptomatic UC had stage T1, T2 and M1 in 30.9%, 16.4% and 2.3%,

respectively. In contrast, patients with asymptomatic UC had stage T1, T2

and M1 in 26.8%, 12.4% and 0.7%, respectively.

Discussion: Patients with symptomatic UC do not dier with regard to

age from those with asymptomatic UC at diagnosis. However, percent-

age of tumor stage UICC 0 was lower and stage UICC IV was higher in

patients with symptomatic compared to those with asymptomatic UC.

Conclusion: e VERSUS study continues to collect epidemiologic and

clinical data of patients with UC.

Disclosure Statement: e authors declare no conict of interest.

880

The cellular dissociation grading system in squamous cell

carcinoma of the penis

Hayel Derani1; Oliver Hakenberg2; Andreas Erbersdobler1

1Universität Rostock, Medizinische Fakultät, Institut für Pathologie, Rostock,

Deutschland

2Universitätsklinikum Rostock: Urologische Klinik und Poliklinik, Rostock,

Deutschland Derani, Hakenberg, Erbersdobler.

Background: e lymph node status (pN) is the most important predic-

tor of survival in patients with invasive penile squamous cell carcinoma

(SCC). Criteria should be identied to improve the prediction of pN. In

this retrospective Study, the cellular dissociation grade (CDG) and WHO

grade (WHO-G) were examined as possible prognostic factors for pN.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts108

Methods: Collective: 101 cases of penile SCC (2014-2020, Rostock

University). e HPF with the highest budding activity and the smallest

nest size of tumor cells was chosen. Tumor bud is dened as a nest with

< 5 tumor cells. Tumor budding (TB) was scored as 1/2/3 according to

number of buds/HPF: 0 / <5 / ≥ 5 . Nest size (ZNG) was scored as 1/2/3/4

aer the number of tumor cells/nest: >15 / 5-15 / 2-4 / 1 . CDG was scored

as 1/2/3 according the sum of (TB+ZNG): 2-3/4-5/6-7.

Results: Comparison of relationship of both grading systems with pN:

Specicity: WHO-G = 0.641, CDG = 0.743. Sensitivity: WHO-G= 0.7 ,

CDG= 0.9 . Negative predictive value: WHO-G = 0.806, CDG= 0.935.

Positive predictive value: WHO-G= 0.5 , CDG= 0.642. P-values for two-

tailed asymptomatic signicance with Pearson’s chi-square test were 0.134

between pN and WHO-G, and 0.001 between pN and CDG. P-values of

the statistical impact on pN were 0.052 for WHO-G und 0.001 for CDG

aer univariate analysis.

Discussion: e CDG had higher prognostic value for pN than the

WHO-G. e sensitivity, specicity, positive and predictive values for pN

were signicantly higher with CDG than with WHO-G. pN showed a sig-

nicant association with CDG, but no signicant association with WHO-

G. ese results are consistent with similar international studies in other

organs.

Conclusion: A grading system with features of tumor budding provides

much better prognostic information than a grading system based on cel-

lular atypia in squamous cell carcinoma of the penis.

Disclosure Statement: e authors declare no conict of interest.

881

An adjusted indirect treatment comparison (ITC) of

enzalutamide (ENZ) versus docetaxel (DOC) for metastatic

hormone-sensitive prostate cancer (mHSPC)

Carsten Ohlmann1; Andrew Armstrong2; Christian Gratzke3;

Jennifer Sugg4; Arijit Ganguli4; Eugen Dornstauder5;

Marco Groß-Langenho5; Reinhard Brauner5; Arnulf Stenzl6

1Johanniter-Krankenhaus Bonn, Bonn, Deutschland

2Duke University, Durham, USA

3Universitätsklinikum Freiburg, Freiburg im Breisgau, Deutschland

4Astellas, Northbrook, USA

5Astellas Pharma GmbH, München, Deutschland

6Eberhard Karls Universität Tübingen, Tübingen, Deutschland

Background: Randomized controlled trials (RCTs) have evaluated ENZ

or DOC vs androgen deprivation therapy (ADT) in patients with mHSPC.

However, no head-to-head RCT has directly evaluated ENZ vs DOC in

mHSPC. is Bucher-adjusted ITC complying with health technol-

ogy assessment (HTA) methods in Germany compared ENZ + ADT vs

DOC + ADT using data from four RCTs with similar study and patient

characteristics.

Methods: HTA inclusion criteria were used to identify mHSPC popula-

tions from four RCTs: the ARCHES and ENZAMET modied intent-to-

treat (mITT) and safety populations, the STAMPEDE M1 ecacy and

modied safety populations, and the CHAARTED ITT ecacy popula-

tion. An adjusted ITC compared ENZ + ADT vs DOC + ADT for over-

all survival (OS) and time to rst serious adverse event (SAE). Several

approaches to account for crossover patients in each RCT were applied.

Result: e ITC included data from 3565 patients for ecacy (OS) and

2766 for tolerability (SAEs) and found a statistically signicant advantage

for ENZ + ADT over DOC + ADT for both OS (HR [95% CI], 0.76 [0.60–

0.95]; p=0.0149) and time to rst SAE (HR [95% CI], 0.10 [0.06–0.16];

p<0.0001). ese advantages were conrmed under each crossover cor-

rection method. e OS advantage of ENZ + ADT over DOC + ADT also

remained signicant (HR [95% CI], 0.76 [0.59–1.00]; p=0.0479) if the ITC

included only data from the ARCHES and STAMPEDE RCTs (N=2153).

Discussion: In the absence of head-to-head RCTs, ITC is an accepted,

valuable method for statistically comparing outcomes from RCTs with

similar designs and patients. Limitations include dierences among RCTs

(eg, patient and disease characteristics) that cannot be fully compensated

by ITC methods and could confound cross-trial comparisons. is analy-

sis did not address outcomes from triplet therapy.

Conclusion: Our study suggests an OS benet of ENZ + ADT vs DOC

+ ADT in patients with mHSPC. RCT data are required to conrm this.

Disclosure Statement: e authors declare no conict of interest.

900

Cardiovascular comorbidities in patients with secondary

malignancies involving the genitourinary tract

Bernhard Koch1; Marcus Bauer2; Lutz Uacker1; Dirk Heimbach3

1St. Vincenz-Krankenhaus, Medizinische Klinik, Innere Medizin 1, Datteln,

Deutschland

2St. Vincenz-Krankenhaus, Medizinische Klinik, Innere Medizin 2, Datteln,

Deutschland

3St. Vincenz-Krankenhaus, Urologische Klinik, Datteln, Deutschland

Background: Cancer associated thrombosis is a potential complication

during the course of a malignant disease which may be related to the

activity of inammatory bystander cells of the tumoral microenvironment

(TME). e participation of TME cells may result in cardiovascular events

(CVE) whose risk may be increased in double maligancies. e propabil-

ity of double malignancies is raised in patients with neoplasms of the gen-

itourinary (GU) tract because prostate and urothelial cancer may occur

synchronously (1) or metachronously, and because urothelial cancer may

reoccur several times at dierent locations during patient`s histories (2).

Methods: We analysed the data bank of our hospital for reports on CVE

in patients with malignancies of the GU tract and related secondary

neoplasms.

Result: In the data set we found 265 patients with malignancies of the

GU-tract with secondary tumors either of other GU-locations or other

organs or malignancies of the hematopoetic (HP) system. In 51 % of these

cases CVE were reported during their lifetime. e correlation was most

obvious in patients with multifocal urothelial cancer. In some cases the

rst manifestations of the CVE were reported preceding the onset of the

malignancy.

Discussion: e remarkable occurence of CVE, which were reported in

patients with secondary malignancies involving the GU-Tract, indicates

the involvement of vascular related phenomena within the development

and course of a malignant process.

Conclusions: e evaluation of comorbidities of patients with secondary

malignancies may help to judge the extent of the contribution of nontu-

moral bystander cells to the course of the malignant process.

References:

1. PMID: 18774459

2. PMID: 26011327

Disclosures: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 109

945

Treatment of Patients with Muscle-Invasive and Metastatic

Bladder Cancer in Germany. Real World Data from the Quality

Assurance Initiative on behalf of the Working

Groups Urological Oncology (AUO) and Medical Oncology

(AIO) of the German Cancer Society (DKG)

Carsten Ohlmann1; Markus Kerkmann2; Laura Holtmann2;

Jürgen Gschwend3; Margitta Retz3; Maike de Wit4

1Klinik für Urologie, Johanniter Krankenhaus Bonn, Bonn,

2MMF GmbH, Münster, Deutschland

3Klinik und Poliklinik für Urologie, Universitätsklinikum rechts der Isar der

Technischen Universität München, München, Deutschland

4Klinik für Innere Medizin, Hämatologie, Onkologie und Palliativmedizin,

Vivantes Klinikum Neukölln, Berlin, Deutschland

Background: e S3-guideline on bladder cancer recommends a rad-

ical cystectomy and a cisplatin-based perioperative chemotherapy

(POC) in patients (pts) with muscle-invasive bladder cancer (MIBC).

Recommendation for metastatic urothelial carcinoma (mUC) is cispla-

tin-based or immuno-oncological (IO) treatment in platinum (Pt) ineligi-

ble pts or as 2nd line therapy. Aim of the study was to obtain representative

data on clinical routine treatment of MIBC and mUC in Germany.

Methods: A nationwide survey was performed to obtain data on stage-re-

lated patient volume in hospitals and oce-based physicians. Based on

these results, a representative sample of treatment data was collected ret-

rospectively from pts records with MIBC and mUC.

Result: Data from 956 pts (MIBC 576; mUC: 380) were collected. 49.8%

of MIBC pts received a systemic therapy, 80.4% of them received cispla-

tin/gemcitabine. 50,2% were treated with a cystectomy without POC.

Signicant factors for cystectomy without POC was higher age >75 years

(Odds ratio (OR) 4.91, 95% CI 3.01-8.11, p<0.001) and Pt ineligible pts

(OR 2.15, 95% CI 1.30-3.59; p=0.003). Treatment decision without inter-

disciplinary tumor board was also correlated with no POC (OR 2.43,

95% CI 1.65-3.61, p<0.001). In mUC Pt pretreated pts are most likely to

receive IO therapy (OR 12.07, 95% CI 6.94-21.82, p<0.001). Other sig-

nicant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71,

p<0.001), higher age > 75 years (OR 2.83, 95% CI 1.43-5.73, p=0.003) and

Pt-ineligible pts (OR 2.57, 95%CI 1.30-5.71, p=0.007).

Discussion: e “gold standard” cisplatin/gemcitabine is established in

Germany if pts are treated with POC. Nonetheless half of the MIBC pts

did not receive a POC, especially if treatment-decision is not discussed in

a tumor board. In mUC IO therapy is established as 2nd line therapy aer

a Pt-based treatment.

Conclusion: Although the guideline recommendations are largely imple-

mented, there is potential for optimization, especially in the establishment

of interdisciplinary tumor boards.

Disclosure Statement: e authors declare no conict of interest.

952

Overall survival with darolutamide versus placebo in

combination with androgen-deprivation therapy and

docetaxel for metastatic hormone-sensitive prostate cancer in

the phase 3 ARASENS trial

Tilman Todenhöfer1; Matthew R. Smith2; Maha Hussain3; Fred Saad4;

Karim Fizazi5; Cora N. Sternberg6; David Crawford7; Evgeny Kopyltsov8;

Chandler H. Park9; Boris Alekseev10; Alvaro Montesa Pino11; Dingwei Ye12;

Francis Parnis13; Teuvo Tammela14; Hiroyoshi Suzuki15; Heikki Joensuu16;

Silke Thiele17; Rui LI18; Iris Kuss17; Bertrand Tombal19

1Studienpraxis Urologie, Nürtigen, Deutschland

2Massachusetts General Hospital Cancer Center, Boston, MA, USA

3Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

4University of Montreal Hospital Center, Montreal, Quebec, Kanada

5Institut Gustave Roussy, University of Paris-Saclay, Villejuif, Frankreich

6Englander Institute for Precision Medicine, Weill Cornell Department of

Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY,

USA

7UC San Diego School of Medicine, San Diego, CA, USA

8Clinical Oncological Dispensary of Omsk Region, Omsk, Russische Föderation

9Norton Cancer Institute, Louisville, KY, USA

10P. Hertsen Moscow Oncology Research Institute, Moscow, Russische

Föderation

11UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y

Virgen Victoria, IBIMA, Málaga, Spanien

12Fudan University Shanghai Cancer Center, Shanghai, Xuhui District, China, VR

13Ashford Cancer Centre Research, Kurralta Park, SA, Australien

14Tampere University Hospital, Tampere, Finnland

15Toho University Sakura Medical Center, Chiba, Japan

16Orion Corporation Orion Pharma, Espoo, Finnland

17Bayer AG, Berlin, Deutschland

18Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ, USA

19Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain,

Brussels, Belgien

Background: Darolutamide (DARO) is a structurally distinct androgen

receptor inhibitor that demonstrated improved overall survival (OS)

and metastasis-free survival vs placebo (PBO) in patients (pts) with

nonmetastatic castration-resistant prostate cancer (CRPC). We inves-

tigated whether DARO in combination with androgen-deprivation

therapy (ADT) + docetaxel would increase OS in pts with metastatic hor-

mone-sensitive prostate cancer (mHSPC) in the ARASENS study.

Methods: is international, double-blind, phase 3 study enrolled pts

who were randomized 1:1 to DARO 600 mg twice daily or matching PBO

in addition to ADT + docetaxel, stratied by extent of disease according

to TNM (M1a-c) and alkaline phosphatase levels. e primary endpoint

was OS. Secondary ecacy endpoints included time to CRPC, time to

pain progression, time to rst symptomatic skeletal event (SSE). Safety

was also assessed.

Result: From Nov 2016 to June 2018, 1306 pts were randomized. At the

primary data cuto (Oct 25, 2021), DARO signicantly decreased the risk

of death by 32.5% vs PBO (HR 0.675, 95% CI 0.568–0.801; P<0.0001). e

signicant OS benet was consistent across prespecied. DARO signi-

cantly delayed time to CRPC versus PBO (HR 0.357, 95% CI 0.302–0.421;

P<0.0001), Time to pain progression (HR, 0.792, 95% CI 0.660–0.950;

P=0.0058) and time to rst SSE. TEAEs were similar between treatment

arms with incidences of the most common TEAEs (≥10%) being highest

during the overlapping docetaxel treatment period, with grade 3/4 TEAEs

of 66.1% for DARO and 63.5% for PBO.

Conclusion: In pts with mHSPC, early treatment combining DARO with

ADT + docetaxel signicantly increased OS and improved key secondary

endpoints vs ADT + docetaxel alone. e incidence of TEAEs was similar

both arms.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts110

Geriatric Oncology

Poster

233

Multicentric validation of a comprehensive geriatric

assessment to predict functional outcome and mortality

following urooncological operations

Christian Fiebig1; Andreas Kahlmeyer2; Hannes Bannert1; Helge Taubert3;

Sven Wach3; Lukas Koneval4; Sebastian Graf5; Decio Maria Folchini6;

Sameh Alalem7; Karl-Günter Gaßmann8; Bernd Wullich3

1Universitätsklinikum Erlangen, Urologische und Kinderurologische Klinik,

Erlangen, Deutschland

2Urologie am Weinberg, Urologische Belegabteilung Elisabeth-Krankenhaus

Kassel, Kassel, Deutschland

3Universitätsklinikum Erlangen, Urologische und Kinderurologische Klinik,

Erlangen, Deutschland

4Universitätsklinikum Würzburg, Klinik und Poliklinik für Urologie und

Kinderurologie, Würzburg, Deutschland

5Kepler Universitätsklinikum, Klinik für Urologie und Andrologie, Linz, Österreich

6Zentralkrankenhaus Bozen, Klinik für Urologie, Bozen, Italien

7SHG-Kliniken Völklingen, Klinik für Urologie, Kinderurologie und urologische

Onkologie, Völklingen, Deutschland

8Malteser Waldkrankenhaus St. Marien, Geriatrie-Zentrum Erlangen, Erlangen,

Deutschland

Background: We present an interim analysis of a multicentric validation

of a novel comprehensive geriatric assessment. is so called ’Erlangen

Index’ (EI) aims to predict the postoperative outcome and mortality of

geriatric cancer patients regarding urooncological operations.

Methods: Prospective observation of patients ≥ 70 years undergoing elec-

tive cystectomy, prostatectomy, or kidney cancer surgery. Preoperatively,

a geriatric assessment was performed. e clinical endpoints were long-

term functional deterioration (Barthel-Index) at days 30 and 180, as well

as mortality at day 180. is assessment is currently performed in four

urological centers (Würzburg, Bozen, Linz, Völklingen) to validate the

the‘EI’.

Result: 159 patients were included in the reference cohort (Erlangen),

106 patients were included in the validation centers. Within the refer-

ence cohort, EI showed a correlation of high-risk patients (EI ≥ 4) with

a functional deterioration at day 30, day 180, and an increased mortality.

Regarding the deterioration of outcome aer 30 days (Würz.: sens=91%,

spec=42%; Linz: sens=74%, spec: 40%) and aer 180 days (Würz.:

sens=50%, spec=91%), similar results were already shown in the valida-

tion centers. In addition, a signicantly reduced survival rate of high-risk

patients can be observed in the reference cohort (χ²(1) = 16.944, p< 0.001)

as well as in the validation centers (χ²(1) = 4.594, p=0.032).

Discussion: In two validation centers (Würzburg and Linz), a preoper-

atively reliable identication of high risk patients can be achieved by the

‘EI’. Due to low numbers of patients recruited at the validation centers

(especially Bozen and Völklingen) so far, no reliable information about

mortality can be displayed.

Conclusion: is rst interim evaluation shows that the so called

‘Erlangen Index’ enables us to identify high-risk cancer patients prior to

operative interventions not only in the reference cohort (Erlangen) but

also in external centers.

Disclosure Statement: e authors declare no conict of interest.

499

Results of the Evaluation of a Complex Supportive

Intervention to Promote Physical Functioning of Older

Patients with Cancer

Eni Shehu1; Sigrid Roggendorf1; André Golla2; Gundula Hübner3;

Gabriele I. Stangl4; Andreas Lau5; Andrea Diestelhorst6; Dirk Vordermark6;

Anke Steckelberg1; Heike Schmidt1,6

1Institute of Health and Nursing Science, Medical Faculty of Martin Luther

University Halle-Wittenberg, Halle (Saale), Deutschland

2Institute of Rehabilitation Medicine, Medical Faculty of Martin Luther University

Halle-Wittenberg, Halle (Saale), Deutschland

3Institute for Psychology, Martin Luther University Halle-Wittenberg, Halle

(Saale), Deutschland

4Institute for Agricultural and Nutritional Science, Martin Luther University Halle-

Wittenberg, Halle (Saale), Deutschland

5Institute of Sport and Sport Science, Martin Luther University Halle-Wittenberg,

Halle (Saale), Deutschland

6Clinic and Outpatient Clinic for Radiotherapy, University Hospital Halle (Saale),

Halle (Saale), Deutschland

Background: In older cancer patients, physical function (PF) may decline

during and aer therapy despite tailoring oncologic therapy to individual

risk factors. erefore, strategies are needed to promote activity and pre-

vent deterioration of daily functioning, self-care and health-related qual-

ity of life (HRQOL).

e project aimed to pilot-test and evaluate a multimodal home-based

intervention to promote PF in older cancer patients during outpatient

radiotherapy, regarding feasibility, acceptance, potential benet of the

intervention and the digital (DI) versus paper-based (PI) instructions.

Methods: Participants underwent assessments of PF at baseline (T0 and

aer 12 weeks, end of the intervention (T1): TUG, 6mWT, chair rise

test, hand strength, physical activity (PA) level (PASE), nutritional status

(BIA), cognition (MMST, clock test), depression (PHQ9), social support

and HRQOL (EORTC QLQ-C30, ELD14). Based on the results and per-

sonal goals they received individual recommendations regarding PA and

nutrition aiming for independent home-based realisation. Aer 16 weeks

current PA, nutrition and HRQOL was assessed (T2).

Results: Participants (n=24, heterogeneous diagnoses, n=14 women,

mean age 70±7 years) were randomized (DI vs. PI). Between time points,

mean values of PF (EORTC QLQ-C30) showed no clinically relevant dif-

ference (>10 pts.) but large individual variance: T0: 77±16, T1: 76±20,

T2: 72±24. Patients appreciated the tailored recommendations and both

formats of instruction. ey reported motivation, social support, positive

eects of the training, activity diary, independent execution of exercises

and pedometers as facilitators. Barriers comprised mainly symptoms e.g.

fatigue, mucositis, pain and radiation side-eects.

Conclusion: e assessment-based tailoring of activity and nutritional

recommendations was appreciated. e unsupervised PA program was

feasible thus providing a possible digitally supported alternative to on-site

training for older patients with cancer especially in rural areas with di-

cult access to the clinic.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 111

788

Treatment in an elderly population ≥ 75 years (yrs.) with

pancreatic ductal adenocarcinoma (PDAC) – Real World Data

(RWD) from the PANDADETECT (PANDA) registry

Daniel Benitez Reinhardt1; Celine Lugnier1; Anna-Lena Kraeft1;

David Witte1; Jens Christmann2; Rabia Safaei1; Peter Leukers1;

Georgia Evripidou1; Thies Lindert1; Nadine Höken1; Inke Feder2;

Magdalena Keller1; Lukas Witkowski1; Monika Janot-Matuschek3;

Orlin Belyaev3; Waldemar Uhl3; Andrea Tannapfel2;

Anke Reinacher-Schick1; Stefanie Nöpel-Dünnebacke1

1Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität

Bochum, Mediznische Klinik V für Hämatologie und Onkologie mit

Palliativmedizin, Bochum, Deutschland

2Institut für Pathologie - Georgius Agricola Stiftung Ruhr, Institut für

Pathologie - der Ruhr-Universität Bochum am Berufsgenossenschaftlichen

Universitätsklinikum Bergmannsheil , Bochum, Deutschland

3Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität

Bochum, Allgemein- und Viszeralchirurgie, Bochum, Deutschland

Purpose: PDAC displays high tumor associated mortality and is rising in

incidence worldwide. With a median age of 72 years (yrs.) it mostly eects

elderly, who are still underrepresented in randomized clinical trials. RWD

could play an increasing role in health care decisions.

Material and Methods: Panda is a monocentric registry capturing clini-

cal data and biomaterial of patients (pts.) with and at risk for PDAC pre-

senting at St. Josef-Hospital, pancreatic cancer center, Ruhr-University

Bochum. We retrospectively compared three age groups (≥75 yrs. (E). vs.

70-74 yrs. (YE) vs. <70 yrs. (Y) diagnosed from 2016 to 2021 concerning

data on treatment modality including surgery and chemotherapy (ctx).

Results: 810 pts. with PDAC were analyzed. Mean age was 66,5 yrs., 428

men and 383 women, Y comprised 471, YE 140 and E 199. 146 pts. (Y/

YE/E: 74/29/43) were resected curatively intended. 347 mPDAC/LAPC

pts. received CTX (Y/YE/E; 209/63/75). Of Y 192 (85%) were recom-

mended to initial therapy with FOLFIRINOX (FFX), of YE 44 (83%)

FFX. Of E 27 (36.0%) received FFX, 29 (38.7%) varying 2-drug combina-

tions,15 (20.0%) monotherapy. Mean age of E primarily recommended to

BSC was 82,4 yrs. (27 pts.).

Discussion:: RWD from Panda comprises pts. ≥75 as 24.5% of enrolled

pts. ough being adequately represented among the pts. receiving resec-

tion, systemic treatment applied varies more than in younger pts. Still, the

majority of E recommended to ctx received combination therapy. 13.6%

of E veriably received just supportive treatment and represent a very old

and possibly frail cohort. Due to retrospective data capture a substantial

number of pts. were lost to documentation.

Conclusion:: Interdisciplinary cancer centers oer intense treatment

options including curative resection for E.

Elderly pts. represent a clinically signicant, yet very heterogenous sub-

group. Since the demand for cancer treatment for elderly patients will

increase within the next decades RWD will be an important source for

tailoring optimized treatment. Data on toxicity, dose reduction and sur-

vival will be presented.

Disclosure Statement: e authors declare no conict of interest.

921

Ecacy and tolerability of uorouracil, leucovorin, oxaliplatin

and docetaxel (ot) in real world patients with advanced

gastric and gastroesophageal cancer: does age really matter?

christian Möhring1, Aliki Timotheou1, Adrianna Mańczak1, Farsaneh Sadeghlar1,

Taotao Zhou1, Robert Mahn1, Alexandra Bartels1, Malte Monin2, Marieta Toma3,

Georg Feldmann2, Peter Brossart2, Mümtaz Köksal4, Gustavo R. Sarria4, Frank A.

Giordano4, Philipp Lingohr5, Azin Jafari5, Jörg C. Kal5, Christian P. Strassburg1,

Maria Angeles Gonzalez-Carmona1

1Universitätsklinik Bonn, Medizinische Klinik und Poliklinik I, Bonn, Deutschland

2Universitätsklinik Bonn, Medizinische Klinik und Poliklinik III, Bonn, Deutschland

3Universitätsklinik Bonn, Institut für Pathologie, Bonn, Deutschland

4Universitätsklinik Bonn, Klinik für Strahlentherapie und Radioonkologie, Bonn,

Deutschland

5Universitätsklinik Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-

und Gefäßchirurgie, Bonn, Deutschland

Background: Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)

regimen has shown strong ecacy as perioperative therapy for patients

with locally advanced gastric (GC) and gastroesophageal (AEG) carci-

noma. In the palliative situation, FLOT is recommended only for young

t patients. Data of ecacy and tolerability of FLOT in elderly patients

are scarce and controversial. us, this study aimed to provide real-life

experience of elderly patients with GC and AEG treated with FLOT as rst

line palliative chemotherapy.

Methods: Patients with advanced or metastatic GC or AEG and treated

with FLOT as rst line palliative therapy between 2010 and 2021 were

analyzed. Patients were grouped into <65-years old (n=35) and ≥65-years

old (n=22) groups. Overall survival (OS), progression free survival (PFS),

feasibility and toxicity were analyzed.

Result: e median OS was 10.4 months with no signicant dierence

between both groups (HR 0.86; 95% CI: 0.48, 1.57; p=0.632). e ECOG

performance status showed powerful inuence on OS in the subgroup

analysis with median OS of 12.3 months for ECOG=0 compared to 5.0

months for ECOG≥1 (p=0.015) as well as in multivariate analysis (HR:

2.62; 95% CI: 1.36, 5.04; p=0.004).

Discussion: e present study suggests a survival benet of the FLOT

regimen as rst-line therapy in a real-life cohort with advanced and met-

astatic GC and AEG. e ECOG performance status showed a stronger

prognostic value than patient age.

Conclusion: In palliative situation FLOT displays an ecient treatment

option for patients with a good ECOG performance status and should

therefore be considered in the therapeutic decision making of elderly

patients with GC and AEG.

Disclosure Statement: Author MG has contributed to advisory boards for Roche,

Eisai, BMS, MSD and AZ. However, these activities have no potential conicts of

interest with the manuscript. None of the other authors have any potential conicts

(nancial, professional or personal) that are relevant to the abstract.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts112

Gynecologic Cancer

Best-of-Abstract-Vortrag

588

The histone H2B monoubiquitination supports aggressive

properties of cervical but not endometrium carcinoma

Florian Wegwitz; Carolin Bast; Sophie Stefanjuk; Sophia Ruckriegl;

Evangelos Prokakis; Carsten Gründker; Julia Gallwas

Department of Gynecology and Obstetrics, University Medical Center

Göttingen, Göttingen, Deutschland

Background: Every year, over 12 000 and 4500 new cases of endome-

trium and cervical carcinoma (EC and CC) are diagnosed in Germany,

respectively. Despite signicant advances in disease management, over

4500 women still succumb yearly to EC or CC. Furthermore, therapies

frequently imply a poorer life quality and a loss of fertility for women of

reproductive age. Previous studies from our group and others demon-

strated an important tumor supportive function of the Histone 2B

monoubiquitination (H2Bub1) epigenetic mark and its E3-Ligase com-

plex (RNF20/RNF40) in several cancers like HER2-positive breast cancer

or colorectal carcinomas. Interestingly, the function of H2Bub1 in EC and

CC has not yet been investigated.

Methods: We took advantage of patient data from e Cancer Atlas

Genome (TCGA) to investigate the potential implication of RNF20 and

RNF40 expression in EC and CC aggressiveness. We next performed in

vitro functional assays to assess the consequence of RNF20 or RNF40 loss

in EC and CC cells. Finally, we ran whole transcriptome analyses to iden-

tify the molecular mechanisms underlying H2Bub1 tumor-supportive

function in CC.

Results: Survival analyses demonstrated that high RNF20 and RNF40

expression correlate with poor prognosis for CC patients but not EC

patients. In line with these ndings, we identied a strong dependency

of CC cells but not EC cells to the H2Bub1-signaling axis in vitro. Our

mRNA-sequencing analysis upon RNF40 knockdown established an

important role of the H2Bub1 signaling supporting epithelial to mesen-

chymal transition and consequently oncogenic properties of CC cells.

Discussion: Our results identied for the rst time H2Bub1 epigene-

tic gene regulation as a central signaling pathway of CC malignancies.

Interestingly, this nding could not be extended to EC entities, underlying

the context specicity of molecular mechanisms driving the aggressive-

ness of cancers.

Conclusion: Targeting the enzymatic activity of the RNF20/RNF40-

complex could represent an attractive opportunity for the development of

novel anti-CC therapies.

Disclosure Statement: e authors declare no conict of interest.

636

OVARIO, A Phase 2 Study of Niraparib + Bevacizumab in

Advanced Ovarian Cancer (OC) Following Front-Line Platinum-

Based Chemotherapy (CT) with Bevacizumab (bev): Updated

Analysis

Melissa. M. Hardesty1; Jacek Grabowski2; Thomas Krivak3; Gail. S. Wright4;

Erika Hamilton5; Evelyn. L. Fleming6; Jimmy Belotte7; Erika Keeton7; Ping

Wang7; Aine Clements8; Heidi. J. Gray9; Gottfried. E. Konecny10; Richard. G.

Moore11; Debra Richardson12

1Alaska Women’s Cancer Care, Anchorage, USA

2Department of Gynecology, Campus Virchow Clinic, Charité Comprehensive

Cancer Center (CCCC), Charité Medical University Berlin, Berlin, Deutschland

3Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,

The Western Pennsylvania Hospital, Pittsburgh, USA

4Florida Cancer Specialists and Research Institute, New Port Richey, USA

5Medical Oncology, Tennessee Oncology, Sarah Cannon Research Institute,

Nashville, USA

6Division of Gynecologic Oncology, Norris Cotton Cancer Center, Dartmouth-

Hitchcock Medical Center, Lebanon, USA

7GlaxoSmithKline, Waltham, USA

8Department of Gynecologic Oncology, Riverside Methodist Hospital,

Columbus, USA

9Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,

University of Washington, Seattle, USA

10University of California Los Angeles, Los Angeles, USA

11Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,

Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, USA

12Division of Gynecologic Oncology, Stephenson Cancer Center, University of

Oklahoma Health Sciences Center, Oklahoma City, USA

Background: Niraparib improved PFS vs placebo in patients (pts) with

newly diagnosed, advanced OC with response to platinum in the PRIMA

trial; niraparib + bev improved PFS vs niraparib in platinum-sensitive

recurrent OC. OVARIO is a single-arm, open-label study evaluating

niraparib + bev treatment aer response to rst-line (1L) platinum-based

CT + bev.

Methods: Eligible pts had newly diagnosed high-grade serous or endo-

metrioid stage IIIB–IV OC with CR, PR, or no evidence of disease aer

1L platinum-based CT + bev; pts could have received neoadjuvant CT or

primary debulking surgery. Tissue testing for homologous recombination

(HR) status was completed at enrollment. Pts received niraparib 200 or

300 mg QD (based on body weight/platelet count) for up to 3 y + bev

15 mg/kg Q3W for up to 22 cycles (including with 1L CT). Endpoints

included 18-mo PFS rate (primary), PFS, OS, safety, tolerability, and

change from baseline in the Functional Assessment of Cancer erapy–

Ovarian Symptoms Index (FOSI) score.

Results: is analysis included 105 pts. At data cuto (June 16, 2021),

median follow-up was 27.6 mo (95% CI 25.5–27.7). Overall, median PFS

(mPFS) was 19.6 mo (95% CI 16.5–25.1). In the HR-decient (HRd) pop-

ulation (n=49), mPFS was 28.3 mo (95% CI 19.9–non-estimable [NE]).

mPFS was 28.3 mo (95% CI 12.1–NE) in the HRd/BRCA-wild-type pop-

ulation (n=16) and NE in the HRd/BRCA-mutant population (n=29). In

the HR-procient population (n=38), mPFS was 14.2 mo (95% CI 8.6–

16.8). e 24-mo PFS rates will be presented at the meeting. In the overall

population, OS was immature with an event rate of 23.8%. FOSI baseline

mean (SD) score was 25.7 (3.79) with a least square mean change from

baseline of −0.7 (95% CI −1.4–0).

Discussion: Niraparib + bev showed promising ecacy following 1L plat-

inum-based CT, with no clinically meaningful impact on quality of life as

assessed by FOSI.

Conclusions:Niraparib + bev 1L maintenance demonstrated promising

results in advanced OC.

Disclosure Statement: e authors declare the following: Funding: GSK study

213358; NCT03326193. Previously presented at SGO 2022, USA (abstract 170);

submitted with permission of authors.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 113

Poster

Neoadjuvant chemotherapy followed by radical surgery

Patients with locally advanced cervical carcinoma in the FIGO

stage IIIb-IVa

Hala Allakeh1; Wladimir Pauker2; David Lazica3; Hilko Strehl4

1DIAKONIEKLINIKUM, Frauenklinik, Assistenzärztin, Rotenburg (Wümme),

Deutschland

2DIAKONIEKLINIKUM, Frauenklinik, Chefarzt, Rotenburg (Wümme), Deutschland

3DIAKONIEKLINIKUM, Urologische Klinik, Chefarzt, Rotenburg (Wümme),

Deutschland

4DIAKONIEKLINIKUM, Strahlenklinik, Chefarzt, Rotenburg (Wümme),

Deutschland

Aim: e locally advanced cervical carcinoma St. III & IV according to

FIGO - selected patients benet from neoadjuvant chemotherapy with

subsequent radical surgery compared to chemoradiotherapy alone.

Methods: three patients with locally advanced cervical cancer were

treated within one year. e patients had histologically clear squamous

cell carcinoma of the cervix uteri, which inltrated the entire cervical

stroma, upper third of the vagina, urinary bladder and parametria on

both sides, up to the pelvic wall and with intra-abdominal suspected of

malignancy LN and hydronephrosis and corresponded to FIGO stage IIIb

and IVa. e patients received 3 cycles of neoadjuvant chemotherapy with

carboplatin (AUC 5) / paclitaxel (175 mg / m2) every three weeks. Aer

down-staging, all patients with a good clinical response to NACT under-

went an interdisciplinary radical operation.

Results: Aer NACT there was a clear improvement in the results with

regard to the reduction in tumor volume, so that all 3 patients were oper-

ated on. One received a radical extended hysterectomy according to Piver

III and the other two according to Piver IV with partial resection of the

urinary bladder and the distal part of the right ureter as well as pelvic and

para-aortic lymphadenectomy. e pathological ndings of the surgical

specimens showed the resected tumor with free resection margins and

tumor-free pelvic and para-aortic lymph nodes. e intra- and postop-

erative time was uncomplicated. e patients then received 6 cycles of

chemoradiotherapy with cisplatin. Aer a mean follow-up of 12 months

(range: 12-24), all patients were free of recurrences and there was no evi-

dence of local pelvic complications.

Summary: e treatment for cervical local advanced cancer in the last

two decades have seen many dierent therapy modalities and what is opti-

mal treatment still controversial. Neoadjuvant chemotherapy followed by

radical surgery for locally advanced cervical CA is a practicable therapeu-

tic strategy with good short- and long-term results in selected patients.

Disclosure Statement: e authors declare no conict of interest.

109

Modied operative therapy for locally advanced vulvar cancer

Wladimir Pauker1; Hala Allakeh1

1AGAPLESION Diakonieklinikum Rotenburg, Frauenklinik, Rotenburg,

Deutschland

Background: modied plastic covering of the vulvar defect aer radical

vulvectomy in locally advanced vulvar cancer to reduce postoperative

wound healing disorders.

Methods: Within two years, 23 patients, mean age 77 years, with locally

advanced vulvar cancer were treated surgically. e patients had histo-

logically conrmed squamous cell carcinoma of the vulva from FIGO

IB (associated / not associated HPV). All tumors were in the area of the

anterior vulva or multifocal as from FIGO IB.Patients receive either a par-

tial or a complete vulvectomy with a modied VU advancement ap as

well as inguinofemoral LNE or sentinel lymphonodectomy on both sides.

edefect covering in the area of the anterior vulva and clitoral region

or the cranial labia minora as a V-shaped drawing of the ap was moved

caudally and sewn in aer the aps had been removed. e defect at the

mons pubis was moved caudally even aer mobilization and thus sutured.

is results in the U-shape compared to the VY advancement ap.

Result: e surgical results with this ap technique for the treatment of

the selected patients are promising: R0 resection of the vulvar cancer, no

postoperative complication rate, so far free of local recurrences and a high

level of patient satisfaction.

Discussion: Especially with oncological indications, it is essential to be

able to treat the oen larger defects aer the histologically conrmed

Intoto-excision of malignant vulvar tumors by means of plastic-recon-

structive surgical procedures.

Conclusion: is technique is very demanding and should be performed

by an experienced surgeon, then based on previous experience, a mini-

mum of postoperative complications can be expected.

Disclosure Statement: e authors declare no conict of interest.

118

The presence of regulatory T-cells and their chemoattractant

CCL22 in endometrial cancer in correlation with overall

survival

Mareike Mannewitz1; Susanne Beyer1; Laura Hahn1; Sarah Meister1;

Konstantin Schnell2; Carolin Perleberg2; David Anz2; Elisa Schmöckel1,3;

Alexander Burges1; Sven Mahner1; Udo Jeschke4; Mirjana Kessler1;

Stefanie Corradini5; Fabian Trillsch1; Thomas Kolben1

1Department of Obstetrics and Gynecology, University Hospital, LMU Munich,

München, Deutschland

2Division of Clinical Pharmacology, University Hospital, LMU Munich, Center of

Integrated Protein Science Munich, München, Deutschland

3Institute of Pathology, University Hospital, LMU Munich, München, Deutschland

4Department of Obstetrics and Gynecology, University Hospital Augsburg,

Augsburg, Deutschland

5Department of Radiation-Oncology, University Hospital, LMU Munich,

München, Deutschland

Background: In Endometrial carcinoma (EC) therapy immunothera-

peutic strategies gain more and more attention. Recruitment of tumor

inltrating regulatory T-cells (Treg) has been shown to have prognos-

tic relevance in a variety of tumor entities by evading the host immune

response. e chemokine CCL22 has been reported as a major attractant

for Treg. Aim of this study is to clarify the mechanistic role and potential

prognostic signicance of CCL22 secretion and Treg in EC.

Methods: A panel of 275 specimens of EC was screened immunohistochem-

ically for the presence of FoxP3+ Treg and CCL22. Immunouorescence

double staining for CCL22 and dierent immune cell markers was per-

formed. Further, a set of functional assays was conducted using the EC cell

lines Ishikawa+ and RL95-2 aer coculturing with isolated Treg in order

to assess their inuence on tumor cell behaviour.

Result: Our results showed that an increased inltration of regulatory

T-cells was associated with reduced overall survival (OS). Coculture of

EC tumor cells with Treg led to an enhanced invasion, migration, and

viability of the tumor cells. High CCL22 staining in tumor cells and the

presence of isolated immune cells in tumor distant areas resulted in a

signicantly increased OS for patients. ese immune cells were charac-

terized as CD68+ and CD80+, concluding they were M1 macrophages.

Conversely a moderate, secretory-appearing staining in the peritumoral

and intratumoral stroma with a worse prognosis.

Discussion: Treg are associated with poorer outcome in women with EC.

e impact of Treg on tumor cell behaviour, favouring especially invasion

and migration, supports the hypothesis that increased levels of FoxP3+

Treg in the tumor microenvironment may promote tumor growth.

Furthermore, our study is the rst investigation of CCL22 in EC and indi-

cated that CCL22 was associated with OS in dependence on its location

and its producing cell type.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts114

Conclusion: Our results provide evidence of Treg as a possible therapeu-

tic target in EC. e impact of CCL22 regarding its dierent localisations

should further be investigated.

Disclosure Statement: e authors declare no conict of interest.

132

Sialyl Lewis X, Sialyl Lewis A and Lewis Y as prognostic factors

in endometrial and cervical cancer

Lena Mueller1; Sophie Mitter1; Mareike Mannewitz1;

Lucia Katharina Keilmann1; Sarah Meister1; Theresa Kolben1;

Elisa Schmoeckel2; Alexander Burges1; Fabian Trillsch1; Bastian Czogalla1;

Udo Jeschke1,3; Mirjana Kessler1; Sven Mahner1; Thomas Kolben1;

Susanne Beyer1

1LMU Munich, University Hospital, Department of Obstetrics and Gynecology,

München, Deutschland

2LMU Munich, University Hospital, Institute of Pathology, München, Deutschland

3University Augsburg, University Hospital, Department of Obstetrics and

Gynecology, Augsburg, Deutschland

Background: Cervical and endometrial cancers are common cancers

worldwide. Several risk factors have been identied and treatment has

been improved in recent years. However, in advanced stages, therapeuti-

cal options are still limited. It has been reported that the expression of the

blood group antigens Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA) and

Lewis Y (LeY) is associated with prognosis in several tumors like breast

cancer.1 Large studies on endometrial and cervical cancer are still missing.

Methods: 234 patients with endometrial cancer (EC) and 244 with cervi-

cal cancer (CC) were included. Specimens were immunohistochemically

stained with antibodies for SLeX und SLeA and LeY. Expression was cor-

related to histopathological variables.

Result: In EC, increased SLeX expression correlated signicantly with

lower pT-stage (p=0.013), low grading (p<0.001), low FIGO-status

(p=0.006) and better overall survival (p= 0.023). High IRS of LeY was

correlated with lower grading (p=0.005) and positive pN (p=0.038) and

worse progression free survival (p=0.022). SLeA expression was higher at

lower pT stage (p=0.013), low grading (p=0.002) and better progression

free survival (p=0.043).

In CC, similar tendencies were shown, but they were not signicant in the

overall collective. However high SLeX expression was signicantly cor-

related with low grading (p=0.029) and pN+ (p=0.032) in patients with

adeno(-squamous) cervical cancer. In squamous cell tumors high LeY

correlated signicantly with better overall (p=0.010) and progression free

survival (p=0.013). No signicant correlation was detected for SLeA.

Discussion and Conclusion: Especially in endometrial cancer, SLeX,

SLeA and LeY were correlated to histopathological parameters and to sur-

vival rates. ese results underline the importance of these blood antigens

as markers for endometrial cancer. Further studies are needed to investi-

gate the underlying processes.

Reference:

1 Jeschke, U. et al. 2005. ‘Expression of sialyl lewis X, sialyl Lewis A, E-cadherin

and cathepsin-D in human breast cancer […]’, Anticancer Res, 25: 1615–22.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

291

SCOUT-1: prospective non-interventional study in BRCA/HRD

tested ovarian cancer (OC) patients eligible for 1L-platinum-

based chemotherapy - Trial in progress

Klaus Pietzner2; Elena Ioana Braicu1; Regina Glowik2; Matthias Rose3;

Pauline Wimberger4; Jalid Sehouli1

1North-Eastern German Society of Gynecological Oncology (NOGGO) and

Department of Gynecology with Center for Oncological Surgery, Charité–

University Medicine of Berlin, Campus Virchow Klinikum, Berlin, Deutschland

2AstraZeneca, Wedel, Deutschland

3Center for Internal Medicine and Dermatology, Department of Psychosomatic

Medicine, Charité-Universitätsmedizin Berlin, Berlin, Deutschland

4Department of Gynecology and Obstetrics, TU Dresden and National Center for

Tumor Diseases (NCT/UCC), Dresden, Deutschland

Background: Two third of patients with OC, have an advanced stage at ini-

tial diagnosis accompanied with poor prognosis. Results from landmark

trials of maintenance therapy (MTX) with poly ADP ribose polymerase

inhibitors (PARPi), especially in tumors associated with homologous

recombination deciency (HRD), like BRCA-mutated tumors, led to the

strong recommendation on testing and treatment procedures in the clini-

cal routine in patients with advanced high-grade epithelial OC. e trans-

lation of these guidelines into clinical routine aects care management

and therefore needs to be evaluated.

Methods: SCOUT-1 is a German prospective, observational study

(NCT04830709; NOGGO ov54) to collect clinical real-world and

patient-reported outcome (PRO) data in patients newly diagnosed with

histologically conrmed advanced (FIGO stage III or IV) high-grade epi-

thelial ovarian, fallopian-tube, or primary peritoneal cancer. Selection cri-

teria include written informed consent, completed surgery (if applicable),

eligible for platinum-based chemotherapy, BRCA1/2 mutation tested and

willingness/ability to report PROs electronically. About 750 patients are

planned to be included in up to 80 hospitals or oce-based sites. Patients

will be followed up for a maximum of 7 years. e primary objective is to

determine the eectiveness of standard treatment sequences by estimating

progression-free survival according to investigator’s assessment. Further

focus is to describe biomarker-testing algorithm, patient selection and to

assess patients’ QoL, symptoms, needs, as well as patients’ expectations.

First subject was included in the study in June 2021. Primary completion

date is planned in Q2 2032.

Indication of source:

1. Presented at 22nd European Congress on Gynecological Oncology (ESGO)

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

294

Alternative sentinel methods in patients with vulvar cancer

Farnaz Jakubek1; Mandy Mangler1; Katharina Vasiljeva1; Joyce

Pullankavunkal1; Natalia Papadopoulos1; Malgorzata Lanowska1

1Vivantes, Gynäkologie, Berlin, Deutschland

Background: In recent studies sentinel lymphonodectomies have been

found to be a feasible method to treat patients with vulvar cancer. Sentinel

detections have been applied in many cancer entities to establish individ-

ualised and targeted concepts in the treatment of cancer patients. Tracing

agents are mostly limited to blue dye only, technetium only, blue dye plus

technetium combined. Agents that have been identied recently have not

yet found their way into national guidelines.

Methods: We describe a case series of 10 patients with vulvar cancer and

sentinel detection with indocyanine green. In all patients sentinel detec-

tion was performed with technetium nanocolloid and blue dye, according

to the conventional protocol described in the national cancer guidelines.

Additionally we applied indocyanin green locally in the vulva to compare

the detection rates.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 115

Results: Indocyanin tracers were easy to apply, the tracers appeared in

the groin lymph nodes within 20-46 minutes aer the application. Near-

infrared uorescence cameras were needed to detect the lymphnodes.

Indocyanin was superior to blue dye in the detection of sentinel nodes.

Discussion: Sentinel lymph node dissection in vulvar cancer patients are

limited, partially due to complicated applications with radioactive agents.

Indocyanine green SLN mapping in vulvar cancer is a new method, with

yet though limited evidence to further individualise and simplify opera-

tive therapy in these women.

Conclusion: Indocyanin is easy to apply, requires no help of radiother-

apists, as it is not radioactive. It has very few side eects and is thus a

feasible alternative to conventional technetium-99m nanocolloid tracers.

Detection rates seem to be superior to the application of blue dye only.

Disclosure Statement: e authors declare no conict of interest.

302

NOGGO ov-42/MAMOC: Rucaparib MAintenance after

Bevacizumab Maintenance following Carboplatin based rst

line chemotherapy in Ovarian Cancer patients

Jalid Sehouli1,2,3; Pauline Wimberger4,5,6,7 8; Jessica Dysarz3;

Angela Relógio9,10; Jens Gerber11; Eva Egger12; Michael Eichbaum13;

Ralf Witteler14; Mustafa Deryal15; Klaus Pietzner1; Radoslav Chekerov1;

Elena Ioana Braicu1,3

1Charité Universitätsmedizin Berlin, Department of Gynecology, Berlin,

Deutschland

2Charité Universitätsmedizin Berlin, European Competence Center for Ovarian

Cancer (EKZE), Berlin, Deutschland

3Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO) e.V.,

Berlin, Deutschland

4Technische Universität Dresden, Department of Gynecology and Obstetrics,

Dresden, Deutschland

5Technische Universität Dresden, Faculty of Medicine and University Hospital

Carl Gustav Carus, Dresden, Deutschland

6Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Deutschland

7National Center for Tumor Diseases (NCT/UCC), Dresden, Deutschland

8German Cancer Research Center (DKFZ), Heidelberg, Deutschland

9Institute for Systems Medicine and MSH-Medical School Hamburg, Hamburg,

Deutschland

10Charité Medical University of Berlin, Institute for Theoretical Biology and

Molecular Cancer Research Center, Berlin, Deutschland

11Städtisches Klinikum Dessau, Clinic for Gynecology and Obstetrics, Dessau-

Roßlau, Deutschland

12Universitätsklinikum Bonn, Department of Gynaecology and Gynaecological

Oncology, Bonn, Deutschland

13Helios Dr. Horst Schmidt Kliniken Wiesbaden, Department of Gynecology and

obstetrics, Wiesbaden, Deutschland

14Universitätsklinikum Münster, Clinic for Gynecology and Obstetrics, Münster,

Deutschland

15CaritasKlinikum Saarbrücken St. Theresia, Center for gynecology, Saarbrücken,

Deutschland

Background: Most ovarian cancer (OC) patients are diagnosed in

advanced stages. Debulking surgery, followed by platinum-based chemo-

therapy and bevacizumab (bev), followed by bev maintenance therapy,

is a therapeutical option for advanced BRCA wild type (BRCAwt) OC

patients in Germany. Despite that 70% of the patients will relapse within

2 years aer diagnosis, prolongation of maintenance therapy might be an

option to improve PFS. Current data showed that bev given longer than

15 months do not translate in better PFS. erefore, in this clinical trial

we aim to analyze the role of sequential maintenance with bev followed

by rucaparib vs bev alone in BRCAwt high grade OC patients. NOGGO

Ov-42/MAMOC trial (NCT04227522) is a phase 3, randomized, place-

bo-controlled study evaluating rucaparib maintenance following bevaci-

zumab maintenance for the treatment of advanced primary high grade

BRCAwt OC.

Methods: 190 BRCA wt patients with histologically conrmed advanced

(FIGO stage IIIA- IV of the 2014 FIGO classication) high grade serous

or high grade endometrioid OC, fallopian tube cancer, primary perito-

neal cancer or clear cell carcinoma of the ovary will be randomized 2:1 to

receive either rucaparib 600mg BID or placebo as maintenance therapy

following rst line chemotherapy with 6 cycles of Carboplatin/Paclitaxel

and at least 12 months of bev given together with chemotherapy and

as maintenance. Randomization is stratied by surgery planned time-

point (neoadjuvant vs. adjuvant), surgical outcome (no residual tumor

massvs. residual tumor mass), response to chemotherapy + bev (CR/

NED vs. PR/SD) and study center. Treatment will continue for 24 months

or until disease progression, unacceptable toxicity, or withdrawal, what-

ever occurs rst. Primary endpoint is PFS per RECIST v1.1. Secondary

endpoints are PFS2, quality of life (EORTC QLQ-C30/OV28, FSI, SF-12,

PROC-CTCAE, Everyday Memory Questionnaire), daily activity, time to

next medical intervention, time to next subsequent therapy, safety assess-

ments and OS. At the moment 14 patients are randomized.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

346

Gynecological cancer patients and their health care

infrastructure during the corona pandemia in Berlin in

2020/21

Malgorzata Lanowska1; Katharina Vasiljeva1; Joyce ; Pullankavunkal1;

Farnaz Jakubek2; Vera Prugger2; Natalia Papadopoulos3; Mandy Mangler2

1Vivantes, Gynäkologie, Berlin, Deutschland

2Vivantes, Gynäkologie, Berlin, Deutshcland

3Vivantes, Gynäkologie, Berlin, Deutschland

Background: Severe unstableness has occurred during the Covid pan-

demic in 2020/21 regarding the accessibility of health care structures.

Patients with symptoms did either not consult their gynecologists, or were

not able to get access to their gynecologists, due to canceled outpatient

consultation hours.

Methods: e rst lockdown due to Covid-19 in Berlin occured in March

2020. We compared the cancer data and cancer patients consultation to

three gynecological centers in three academic hospitals in Berlin in the

years 2018/2019 to 2020/2021. Consultations and stages of tumors in 840

patients were compared and matched monthly between the years.

Result: In the rst lockdown March 2020- June 2020 20% less cancer

patients consultated our clinics. e results were found to be signicant.

Elder patients did tend to consult the health care system less during the

lockdown as compared to before the lockdown.

In the rst lockdown March 2020- June 2020 20% less cancer patients con-

sultated our clinics. e results were found to be signicant. Elder patients

did tend to consult the health care system less during the lockdown as

compared to before the lockdown.

Aer the rst lockdown a tendency to more advanced cancer stages were

observed in the cancer patients.

Discussion: During the Covid-19 pandemic medical care for cancer

patients was impaired, as compared to the time before the pandemic.

Signicantly less patients consulted the health care system and found sup-

port for their symptoms.

Conclusion: e alterations due to the pandemic will, most probably,

aect the long term survival of these cancer patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts116

347

Expression of the adipokine chemerin and its receptor

chemokine-like receptor 1 (CMKLR1) in ovarian cancer

Susanne Schüler-Toprak1; Florian Weber2; Christa Büchler3;

Olaf Ortmann1; Oliver Treeck1

1Department of Gynecology and Obstetrics, University Medical Center

Regensburg, Regensburg, Deutschland

2Department of Pathology, University of Regensburg, Regensburg, Deutschland

3Department of Internal Medicine I, University Medical Center Regensburg,

Regensburg, Deutschland

Background: e multifunctional adipokine chemerin plays an import-

ant role in several cancer types. Here, we investigated the role of chemerin

and its receptor CMKLR1 in ovarian cancer (OC). Protein expression of

chemerin and CMKLR1 in OC was assessed and correlated with OC mark-

ers, steroid hormone receptors and cancer-associated genes. Additionally,

we examined the inuence of the expression of chemerin and its receptor

on survival of OC patients.

Methods: For this purpose, we established a tissue microarray from 153

OC patients and performed immunohistochemical analyses.

Result: Chemerin was found to positively correlate with progesterone

receptor (p<0.0001), CEA (p=0.0428), as well as with nuclear and cyto-

plasmic estrogen receptor β; (p=0.0213 and p=0.0029, respectively)) in

serous OCs. Moreover, a strong positive correlation was found between

chemerin and estrogen related receptors (ERR) α, β and γ (p< 0.0001,

p=0.0007 and p< 0.0001, respectively) in all OCs as well as in the serous

subtype. Also CMKLR1 was shown to strongly correlate with expression

of ERR α, β and γ in all OC cases and in the serous subtype. Survival

analyses revealed that chemerin expression did not aect overall (OS) or

progression-free survival of OC patients. However, higher expression of

CMKLR1 in low grade OCs indicated signicantly decreased OS com-

pared to those with lower levels of CMKLR1 (p<0.05).

Discussion: Our data underline a role of chemerin and its receptor in OC

development as we observed correlations of chemerin with the expression

of several steroid receptors and OC markers as well as an association of

CMKLR1 with survival.

Conclusion: Our data suggest an important role of chemerin and its

receptor in OC.

Disclosure Statement: e authors declare no conict of interest.

351

Precancerous lesions in patients with abnormal PAP smear

Malgorzata Lanowska1; Vera Prugger2; Natalia Papadopoulos1;

Katharina Vasiljeva1; Farnaz Jakubek2; Joyce Pullankavunkal1;

Mandy Mangler2

1Vivantes, Gynäkologie, Berlin, Deutschland

2Vivantes, Gynäkologie, Berlin, Deutschland

Background: e appearance of precancerous lesions of the cervix due

to HPV infection is known to be related to pathological ndings in pap

smears. Pap smears are classied in ve dierent groups Pap I-V.

Inconsistent results between pap smears and histological ndings trouble

the reliability of pap smears.

Methods: Data of 1500 patients who were referred to our oncological cen-

ter in 2020 and 2021 to undergo colposcopy and pathological validation

due to pathological pap smears or HPV infection was analysed.

Results: Pap smears were correlated with histopathological dysplasia to

dierent extents: in high grade dysplasia 14% of patients showed unsus-

picious or slightly changed pap smear results: Pap I 5.8%, Pap IIg,p,e in

8.3%. e rest 86% was unevenly spread. Pap IIIp was found in 11,2%, Pap

IIID1 in 16,1%, Pap IIID2 in 33,9% of the women.

Pap IV, commonly directly correlated to high grade dysplasia, could only

be proven in 20% of the pap smears analysed: Pap Iva-p 19.5% and Pap

IVb-p 1.7%

Discussion: Pap smears are used as a screening method in Germany to

detect low and high grade lesions and cervical cancer. ese pap smears

seem to have an inconsistent reliability to nd histological precancerous

lesions.

Conclusion: us, PAP smears alone have a low prediction rate for the

presence of dysplasia and should be combined with other methods before

initiating therapy.

Disclosure Statement: e authors declare no conict of interest.

397

iKNOW - Development and evaluation of an online tool for

counseling BRCA1/2 mutation carriers

Caren Hilger1; Friederike Kendel1; Maren Heibges2; Christine Schmid2;

Markus Feufel2; Dorothee Speiser3

1Charité – Universitätsmedizin Berlin, Geschlechterforschung in der Medizin

(GiM), Berlin, Deutschland

2Technische Universität Berlin, Institut für Psychologie und Arbeitswissenschaft,

Fachgebiet Arbeitswissenschaft, Berlin, Deutschland

3Charité – Universitätsmedizin Berlin, Klinik für Gynäkologie mit Brustzentrum,

Zentrum Familiärer Brust- und Eierstockkrebs, Berlin, Deutschland

Background: Women carrying BRCA1/2 gene mutations have markedly

increased lifetime risk of breast/ovarian cancer. Medical consultation

poses challenges for physicians and women seeking advice: Physicians

have to communicate complex information in a comprehensible way to

enable preference sensitive decisions. Women need to understand their

individual cancer risks to make informed decisions to achieve optimal

risk management.

Aim: We developed the evidence-based online counseling tool iKNOW to

support consultation of BRCA mutation carriers in direct doctor-patient

conversation and as individual reference book for counselees.

Method: In an RCT, participants received either counseling using iKNOW

or standard consultation. At four measuring points (T0=before consulta-

tion; T1=immediately aerwards; T2=four weeks; T3=six months aer

consultation), participants received self-report questionnaires including

items on risk understanding. χ2-tests and robust Mann-Whitney U-tests

were used to compare participants in the intervention group with the con-

trol group.

Results: At baseline, N=220 women participated in the study. Of those,

n=108 were counseled using iKNOW, n=112 received standard con-

sultation. Of the total sample, 140 women (63.6%) were BRCA1 carriers

and 80 (36.4%) carried a pathogenic variant in BRCA2. e distribution

did not dier between intervention and control group. Data collection is

currently ongoing and will be completed in October 2021. Results on risk

understanding can be presented in 2022.

Outlook: If evaluation is successful, the counseling tool will be adopted

into standard care and its content can be regularly adapted to current

evidence.

Disclosure Statement: e authors declare no conict of interest.

398

Impact of COVID-19 pandemic on the treatment of cervical

cancer in Hessian hospitals– a population-based study

Petra Neuser1; Heiko Müller2; Anne Byl3; Nora Bamberger3; Martin Rapp3;

Soo-Zin Kim-Wanner1

1Hessisches Krebregister, Hessisches Landesprüfungs- und Untersuchungsamt

im Gesundheitswesen, Landeauswertungsstelle, Frankfurt, Deutschland

2HA Hessen Agentur GmbH, Wiesbaden, Deutschland

3Hessisches Krebsregister, Vertrauensstelle, Frankfurt, Deutschland

Background: During the Covid-19 (Cov19) pandemic hospitals were

assigned to four levels according their resources to manage the increased

demand of intensive care treatments. is study aims to contribute

towards quantifying the impact of the Cov19 pandemic on cancer care of

patients with cervical cancer in Germany by investigating the diagnoses

and treatments in Hessian hospitals of dierent Cov19 levels.

Methods: Data of patients with cervical cancer (C53) diagnosed from

2016 to 2020, were extracted from the database of the Hessian cancer

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 117

registry. With regard to a continuously stable registration activity eleven

hospitals were included in the analysis. Seven hospitals met the criteria for

Cov19 level 1 (highest requirements) and four hospitals for level 2.

Result: In 2020, 31% fewer patients with cervical cancer were diag-

nosed in eleven Hessian hospitals compared to previous years (n=124 vs.

n=179). Primary tumor resections were reduced by 24%, whereas no dif-

ference could be detected in their relative amount or timespan from diag-

nosis. e patient cohort was younger with a median age of 46 vs. 50 years

and with early stage I-II in 70% vs. 62%. e reduction in treatment was

mostly seen in the Cov19 level 1 hospitals, while level 2 hospitals could

increase the amount of diagnosed (14%) and treated (27%) patients.

Discussion: Despite a reduction of diagnoses and treatments, primary

surgery was not delayed. e patient characteristics imply that predomi-

nantly elder women with advanced stages omitted hospital treatment. e

increased burden of care of Cov19 patients for the level 1 hospitals clearly

had an impact on the care of cancer patients, which could be partially

absorbed by level 2 hospitals.

Conclusion: Reorganisation of hospitals according to Cov19 levels was an

important tool to enable treatment of Cov19 patients while maintaining

cancer care by shiing treatment to other hospitals. However, there is an

impact on missed diagnoses and treatments of patients, that will result in

a higher morbidity and mortality.

Disclosure Statement: e authors declare no conict of interest.

565

The Role of DAPK1 in the Cell Cycle Regulation of Cervical

Cancer Cells and in Response to Topotecan

Khayal Gasimli1; Monika Raab1; Sven Becker1; Mourad Sanhaji1;

Klaus Strebhardt1,2

1Universitätsklinikum Frankfurt, Gynäkologie und Geburtshilfe, Frankfurt am

Main, Deutschland

2Deutsches Krebsforschungszentrum, Partner facility Frankfurt, Frankfurt,

Deutschland

Introduction/Background:Cervical cancer is one of the most serious

health conditions, with nearly 500,000 women developing the disease

each year worldwide. At present, the treatment of recurrent cervical can-

cer remains largely ineective, and eorts in cancer drug development are

currently focused on critical serine/threonine kinases, such as death-as-

sociated protein kinase 1 (DAPK1) and polo-like kinase 1 (PLK1). In the

current study, we aimed at exploring the cell cycle roles of DAPK1 and

PLK1 in cervical cancer cells.

Methods: Multiple methods including western blotting and assays were

used for studying kinase activity, apoptosis, cell cycle, cell proliferation,

immunouorescence and proximity ligation.

Result(s):e present study demonstrated that, in cervical cancer cells, the

enzymatic activity of DAPK1 was regulated in a cell cycle-specic man-

ner. NIMA-related kinases, CDKs, PLKs and Aurora kinases regulate the

function of centrosomes by orchestrating the separation of chromosomes

during cell division. e present study added DAPK1 to this group of pro-

tein kinases due to its localization at centrosomes during mitosis. It was

shown that DAPK1 was autophosphorylated at Ser308 in the G2phase and

during mitosis. From prophase to metaphase, the colocalization of PLK1

and DAPK1 at centrosomes was observed. Furthermore, the interaction of

both these kinases could be demonstrated using proximity ligations assays

and immunoprecipitations. DAPK1 was found to be a substrate of PLK1.

Topotecan is an eective drug used for the treatment of cervical cancer.

Conclusion:e current study examined the role of DAPK1 in topote-

can-induced cervical cancer cell death, and it was identied that RNA

interference-based silencing of DAPK1 decreased the apoptotic eect of

topotecan. us, these ndings suggested that DAPK1 could be a bio-

marker and a potential target for the response to topotecan during the

therapy of patients with cervical cancer.

Disclosure Statement: e authors declare no conict of interest.

571

RIG-I as a potential new target for immunotherapies in

endometrial cancer

Sophie Mitter1; Lena Müller1; Mareike Mannewitz1; Sarah Meister1;

Theresa Kolben1; Elisa Schmoeckel2; Alexander Burges1; Bastian Czogalla1;

Anna Hester1; Sven Mahner1; Udo Jeschke1,3; Stefanie Corradini4;

Fabian Trillsch1; Mirjana Kessler1; Thomas Kolben1; Susanne Beyer1

1Department of Obstetrics and Gynecology, University Hospital, LMU Munich,

Germany

2Institute of Pathology, University Hospital, LMU Munich, Germany

3Department of Obstetrics and Gynecology, University Hospital Augsburg,

Augsburg, Germany

4Department of Radiation-Oncology, University Hospital, LMU Munich, Munich,

Germany

Background: RIG-I (retinoic acid inducible gene I) increases expression

and secretion of type-I-interferons, leading to recruitment of immune

cells and induction of apoptosis. RIG-I is attributed a tumor-suppressive

eect in various tumor entities such as melanoma. For endometrial cancer

(EC), one of the most common gynecological malignancies and an immu-

nogenic cancer, data about RIG-I as part of the innate immune system are

missing. Our aim is to investigate the relationship between RIG-I expres-

sion and outcome in patients with EC.

Methods: Immunohistochemical staining was performed on 225 spec-

imens of patients with EC. RIG-I expression was correlated with histo-

pathological and survival data.

Result: Elevated RIG-I levels correlated positively with advanced tumor

stage and poor grading (FIGO stage p=0.027; T stage p=0.010; grading

p=0.007). Overall survival was shorter in patients with high RIG-I levels

(p=0.009). Furthermore, RIG-I was found to be an independent negative

predictor of progression-free survival (p=0.022).

Discussion and Conclusion: Our data establish RIG-I as a new marker

for outcome in patients with EC. Compared to most other tumor entities

where RIG-I seems to be tumorsuppressive, higher RIG-I-expression is

associated with exactly the opposite eect in EC. In further studies, we are

investigating the underlying mechanisms in more detail.

Disclosure Statement: e authors declare no conict of interest.

580

Targeting of the Polo-like kinase 1 (PLK1) to improve the

eciency of Olaparib in BRCA mutated epithelial ovarian

cancer

Khayal Gasimli1; Morva Tahmasbi Rad1; Monika Raab1; Sven Becker1;

Elisabeth Kurunci-Csacsko1; Klaus Strebhardt1,2; Mourad Sanhaji1

1Universitätsklinikum Frankfurt, Gynäkologie und Geburtshilfe, Frankfurt am

Main, Deutschland

2German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, Frankfurt

am Main, Deutschland

Background: Currently, the treatment of epithelial ovarian cancer (EOC)

remains largely ineective, and recurrent resistance to platinum-based

chemotherapy represents the major challenge in EOC management.

Emerging data report that BRCA-mutated cancers may also resist PARPi.

PLK1 is a crucial regulator of cell cycle progression. Its protein expression

is signicantly elevated in ovarian cancers.

Methods: To explore the role of PLK1 in sensitizing EOC cells, OVSAHO

and KURAMOCHI, and patient derived 3D-spheroids underwent a

mono- or a combination therapy using the PLK1 inhibitor BI6727, the

PARP inhibitor Olaparib, and Carboplatin. e cell survival upon the

treatments was investigated using the 2D clonogenic assay. In addition, the

cell death triggered by the dierent treatment conditions has been inves-

tigated by assessing the enzymatic activation of the eector caspases 3/7

(Caspase 3/7 Glo assay) and using Annexin/AAD staining. Additionally,

the eects of the mono and the combinatorial treatments on the growth of

the BRCA-mutated cell lines-based 3D-spheroids were evaluated by mea-

suring the spheroid volumes aer a dened period post treatment.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts118

Result: Our study shows that PLK1 inhibition with the specic inhibi-

tor BI6727 triggers a robust sensitization of ovarian cancer with BRCA-

mutations and patient derived cancer cells to Olaparib. Furthermore,

the combination of Olaparib and BI6727 signicantly reduced the

survival of ovarian cancer cells in 2D and 3D cell models upon plati-

num-based chemotherapy, initiates mitochondrial apoptosis by inactivat-

ing the anti-apoptotic BCL-2 family proteins, followed by activation of

caspase-dependent eector pathways. We found that that PLK1 inhibition

signicantly strengthens Olaparib-associated cell death in BRCA-mutated

EOC, supporting the translation of this combination, Olaparib/ BI6727,

into a clinical trial.

Conclusion: Our ndings elucidate the critical role of PLK1 in the resis-

tance to PARPi in BRCA-mutated EOC and suggest a new combinatorial

strategy that may improve platinum-based ecacy.

Disclosure Statement: e authors declare no conict of interest.

620

Poor sialic acids moieties on glycosphingolipids conduct

metastatic formation in ovarian cancer

Cecile Cumin1; Arun Everest-Dass2; Yen-Lin Huang1; Charlotte Rossdam3;

Natalie Rimmer1; Ching-Yeu Liang1; Monica Nunez-Lopez1;

Viola Heinzelmann-Schwarz1,4; Falk Buettner3; Francis Jacob1

1University Hospital Basel, Ovarian Cancer Research, Department of

Biomedicine, Basel, Schweiz

2Grith University, Institute for Glycomics, Gold Coast, Australien

3Hannover Medical School, Institute for Clinical Biochemistry, Hannover,

Deutschland

4University Hospital Basel, Hospital for Women, Department of Gynecology and

Gynecological Oncology, Basel, Schweiz

Background: To invade the peritoneal cavity and form metastatic sites,

ovarian cancer cells need to undergo reversible epithelial-to-mesenchy-

mal transition (EMT/MET). Here, depletion of globosides (ΔA4GALT),

a subclass of glycosphingolipids (GSLs) has been aliated with EMT-

associated ovarian cancer spreading [1]. However, the GSL-mediated

mechanism contributing to primary and metastatic formation remains

unclear.

Methods: We rst investigated intra-patient heterogeneity for E-cadherin

and GSLs using tissue microarrays with matched samples and MALDI-

MSI, respectively. Bulk and single cell transcriptomic datasets were

assessed to align GSL-encoding gene with EMT marker expression. us,

the identied ganglioside synthesizing enzyme ST8SIA1 was homozy-

gously knocked out using CRISPR-Cas9, validated by xCGE-LIF, in vitro

and in vivo assays. Associated signaling pathways were dissected by (phos-

pho-) proteomic analysis.

Results & Discussion: E-cadherin was persistently expressed in the

tumor compartment independent of the time of disease and showed co-

expression with globosides while gangliosides were associated to the mes-

enchymal-like stroma. Genetic deletion of ST8SIA1 (ΔST8SIA1) reduced

the expression of mesenchymal (Vimentin) and increased epithelial mark-

ers (E-cadherin, Claudin 1&3). Interestingly, loss of sialic acids on gan-

gliosides reduced the cell capacity migrate (p < 0.05) but increased their

competence to form spheroids in 3D cultures (p < 0.05) and tumor growth

in tumor xenogras. In contrast, loss of globosides in ΔA4GALT cells

demonstrated an invasive behavior. Finally, phosphoproteomics identied

a decrease of phosphorylation of peptides such as MTOR, MAPK1 and

AKT in ΔST8SIA1 which is usually associated with MET while pathways

related to calcium were enriched in ΔA4GALT cells.

Conclusion: We provide the rst evidence that GSLs play an important

role in EMT and MET. ese data suggest that sialic acid -rich GSLs may

be an important driver of EMT-associated pathways.

Reference:

1. Jacob et al. Cancer Res. 2018, 78(11):2952-2965. PMID: 29572228

Disclosure Statement: e authors declare no conict of interest.

629

NK cell-mediated eradication of ovarian cancer cells with a

novel chimeric antigen receptor directed against CD44

Jens Hachenberg1,2; Katharina Zimmermann2; Michael Morgan2;

Peter Hillemanns1; Axel Schambach2; Rüdiger Klapdor1,2

1Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und

Geburtshilfe, Hannover, Deutschland

2Medizinische Hochschule Hannover, Institut für experimentelle Hämatologie,

Hannover, Deutschland

Background: Despite advances in adjuvant therapy, most ovarian cancer

(OC) patients suer from recurrent disease. Ovarian cancer stem cells

(CSC) represent a source of tumor recurrence. CSC are characterized by

high resistance to chemotherapy and enhanced tumorigenicity. Chimeric

antigen receptor (CAR)-based adoptive immunotherapy represents a

promising strategy to reduce the risk for recurrent disease. We evaluated a

third-generation CAR against CD44, an ovarian CSC marker.

Methods: We used OC cell lines A2780, SKOV3, and OVCAR3 as well as

primary OC cells. We generated an anti-CD44 CAR based on a third-gen-

eration CAR design containing CD28 and 4-1BB as co-stimulatory

domains. NK-92 cells were equipped with the novel CAR constructs by

lentiviral transduction. We performed IFNγ release assays to demonstrate

specic activation of engineered NK cells. Live cell impedance analysis

with xCELLigence was used to estimate the anti-tumor activity of NK

cells. NK cells and cisplatin were added to A2780 or primary OC cells

to investigate the feasibility of this combination. Aer treatment, analy-

sis was accomplished using the CellTiter 96® AQueous One Solution Cell

Proliferation Assay.

Result: NK-92 cells equipped with the anti-CD44 CAR (CD44NK)

showed specic cytotoxic activity against CD44-positive OC cells and

primary OC cells. IFNγ secretion assays indicated specic activation of

the engineered cells aer incubation with target cells. Additionally, we

evaluated the treatment combinations of CD44NK cells and cisplatin.

e simultaneous treatment with CD44NK and cisplatin showed higher

anti-tumor activity compared to sequential treatment.

Conclusion: e new anti-CD44 CAR exhibited specic killing in OC

cell lines and primary OC cells. CD44NK cells retained their cytotoxic-

ity during cisplatin incubation. e most potent anti-tumor eect was

achieved by simultaneous treatment with CD44NK cells and cisplatin.

is study will be the basis for further in vivo studies and future clinical

developments.

Disclosure Statement: e authors declare no conict of interest.

640

A functional CRISPR screen to determine PARP inhibitor

sensitivity in ovarian cancer

Ricardo Coelho1; Muriel Disler1,2; Alessandra Tozzi1,2; André Fedier1; Viola

Heinzelmann-Schwarz1,2; Francis Jacob1

1University Hospital Basel, Department of Biomedicine, Ovarian Cancer

Research, Basel, Schweiz

2University Hospital Basel, Gynecological Cancer Center, Hospital for Women,

Basel, Schweiz

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have

transformed the therapeutic landscape of high-grade serous ovarian

cancer. Maintenance strategies with PARPi have been assessed in vari-

ous clinical trials and shown improvement in progression-free survival

for carriers of BRCA1/2 mutation1,2. Interestingly, these data also point

towards an extended benet of PARPi for patients with homologous

recombination (HR)- deciency beyond BRCA1/2 alterations. erefore,

there is an urgent need to unveil “true” predictive biomarkers for PARPi

response.

Methods: Design and lentivirus deliver of sgRNAs targeting candidate

genes (n=21) into Cas9+ ovarian cancer cell lines (n=5) together with

Olaparib-PARPi selective pressure. Target genes were selected based on its

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 119

role of cancer “cell tness” and involvement in HR repair pathway identi-

ed by a literature-based search and publicly available data from Cancer

Cell line Encyclopedia.

Results/Discussion: Despite variations in “cell tness”, a cell line-inde-

pendent sensitivity to Olaparib was observed for the genomic disruption

of BRCA1/2 in all cell lines tested. In contrast, genes such as ATM, RAD51,

RAD51B, RAD51C, RAD51D, XRCC3 and XRCC2 revealed a cell line-de-

pendent dropout rate suggesting that several HR repair-related genes

depend on additional factors to confer Olaparib sensitivity.

Conclusions: We established a functional CRISPR screen and identied

genes conferring sensitivity to Olaparib shedding light on the importance

of a functional assay to identify “true” predictive biomarkers. Ongoing

work investigates gene dependencies in regards to dierent PARPi and its

translation in patient-derived tissue samples.

References:

1 Gonzalez-Martin, A. et al. Niraparib in Patients with Newly Diagnosed

Advanced Ovarian Cancer. N Engl J Med 381, 2391-2402, doi:10.1056/

NEJMoa1910962 (2019).

2 Moore, K. et al. Maintenance Olaparib in Patients with Newly Diagnosed

Advanced Ovarian Cancer. N Engl J Med 379, 2495-2505, doi:10.1056/

NEJMoa1810858 (2018).

Disclosure Statement: e authors declare no conict of interest.

654

Niraparib ecacy and safety in patients with BRCA-mutated

(BRCAm) ovarian cancer: results from three phase 3 niraparib

trials

Antonio González-Martín1,2; Jacek Grabowski3; Ursula Matulonis4;

Jacob Korach5; Mansoor Mirza6; Kathleen Moore7; Divya Gupta8;

Stanislav Lechpammer8; Bradley J Monk9

1Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spanien

2Clínica Universidad de Navarra, Madrid, Spanien

3Campus Virchow Clinic, Charité Comprehensive Cancer Center (CCCC), Charité

Medical University Berlin, Berlin, Deutschland

4Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA

5Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv,

Israel

6Rigshospitalet, Copenhagen University Hospital, Copenhagen, Dänemark

7Stephenson Cancer Center, University of Oklahoma Health Science Center,

Oklahoma City, USA

8GlaxoSmithKline, Waltham, USA

9Arizona Oncology (US Oncology Network), University of Arizona College of

Medicine, Creighton University School of Medicine, Arizona, USA

Background: Niraparib is approved for the maintenance treatment

of patients (pts) with advanced or recurrent ovarian, fallopian tube, or

primary peritoneal cancer (OC) aer chemotherapy (CT). Here, we

summarize niraparib ecacy and safety in pts with BRCAm OC across

three phase 3 trials: PRIMA/ENGOT-OV26/GOG-3012 (PRIMA;

NCT02655016), ENGOT-OV16/NOVA (NOVA; NCT01847274), and

NORA (NCT03705156).

Methods: Pts enrolled in PRIMA had newly diagnosed advanced OC. All

pts had stage III/IV high-grade serous or endometrioid tumors and had

a complete or partial response to rst-line platinum-based CT. Subgroup

analysis by tumor BRCAm status was prespecied. Pts enrolled in NOVA

and NORA had platinum-sensitive, high-grade serous OC and received

≥2 lines of platinum-based CT. In both studies, subgroup analysis by ger-

mline BRCAm status was prespecied. e primary endpoint in all tri-

als was progression-free survival (PFS) by blinded independent central

review.

Results: e BRCAm populations from each trial are as follows: 223

(148 BRCA1m and 75 BRCA2m) from PRIMA, 203 (128 BRCA1m, 69

BRCA2m, and 13 BRCA1/2m) from NOVA, and 100 (78 BRCA1m,

21 BRCA2m, and 1 BRCA1/2m) from NORA. In PRIMA, median PFS

(mPFS) was 22.1 vs 10.9 mo with niraparib vs placebo (PBO) in BRCAm

pts (hazard ratio [HR] 0.40, 95% CI 0.27–0.62). In gBRCAm pts in NOVA,

mPFS was 21.0 vs 5.5 mo with niraparib vs PBO (HR 0.27, 95% CI

0.17–0.41). In NORA, mPFS was not reached in gBRCAm pts receiving

niraparib and was 5.5 mo with PBO (HR 0.22, 95% CI 0.12–0.39). mPFS

HRs (95% CI) in pts with BRCA1m and BRCA2m in PRIMA were 0.39

(0.23–0.66) and 0.35 (0.15–0.84), respectively. Across the 3 trials, the most

common treatment-emergent adverse events were thrombocytopenia,

anemia, neutropenia, and hypertension.

Conclusion: Patients with BRCAm OC derived a signicant PFS benet

from niraparib maintenance treatment across all 3 trials. No new safety

signals were identied.

permission.

Disclosure Statement: e authors declare the following: Funding: NOVA

(213356)/PRIMA (213359), GSK; NORA, Zai Labs.

662

Validation of epigenetic and genetic alterations of ITIH5 in

cervical scrapes

Lisa-Marie Lipfert1; Nadja Ziller1; Angelique Ziegfeld1; Stefanie Schütze1;

Julia Vorwergk1; Katrin Beer1; Mieczyslaw Romuald Gajda2;

Anita Homann2; Nicolaus Gaßler2; Ingo B. Runnebaum1; Matthias Dürst1;

Claudia Backsch1

1Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,

Universitätsklinikum , Jena, Deutschland

2Sektion Pathologie des Instituts für Rechtsmedizin, Universitätsklinikum, Jena,

Deutschland

Purpose: Progression of human papillomavirus-induced premalignant

cervical intraepithelial neoplasia (CIN) to cervical cancer is driven by

epi(genetic) events. Previous studies revealed a progressive down-regula-

tion of the gene ITIH5 in the course of cervical carcinogenesis. Promoter

methylation in conjunction with deletions in the gene region of ITIH5

seem to be contribute to notable ITIH5 downregulation as shown in in

vitro studies using cervical cancer cell lines and cryosections of cervical

lesions. Aim of the current study is to validate (epi)genetic alterations of

ITIH5 in cervical scrapes of CIN of dierent severity.

Methods: In order to investigate the genetic status of ITIH5, cervical

scrapes of patients with histologically conrmed low grade lesions (CIN1)

(n=20) and high grade lesions (CIN2-3) (n=60) are analysed using a

locus-specic probe for ITIH5 and a control probe for centromere 10 for

direct interphase uorescence in situ hybridization. In parallel, ITIH5

promoter methylation is investigated by qualitative and quantitative

methylation specic PCR in the same clinical samples.

Results: Preliminary results for CIN2-3 showed a higher number of cases

with copy number loss of ITIH5 as well as ITIH5 DNA methylation com-

pared to CIN1. Additionally, in some cases of CIN2-3 a loss of centromere

10 was detected. Investigations are still ongoing.

Conclusions: A combined screening of the copy number state of ITIH5

and the methylation pattern may help in the early detection of human

papillomavirus- induced genetic instabilities and genetic modications

and may be useful as novel molecular markers for progression of CIN.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts120

663

Constitutive BRCA1 promoter methylation in early-onset

ovarian cancer

Johanna Schmolling1; Jan Hauke1; Alexander Volk2; Dimo Dietrich3;

Mohamad Kayali1; Sandra Schmidt1; Rita Katharina Schmutzler1;

Eric Hahnen1

1Uniklinik Köln, Zentrum Familiärer Brust- und Eierstockkrebs, Köln, Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Institut für Humangenetik,

Hamburg, Deutschland

3Universitätsklinikum Bonn, Klinik und Poliklinik für Hals-Nasen-Ohren-

Heilkunde, Bonn, Deutschland

Background: e prevalence of germline BRCA1/2 (gBRCA1/2) muta-

tions in patients with early-onset ovarian cancer (OC) is compara-

tively low. Of the patients documented in the German Consortium for

Hereditary Breast and Ovarian Cancer (GC-HBOC) registry, 35/433 OC

patients with an onset ≤35 years carried gBRCA1/2 mutations (8.1%); this

proportion increased to 20.0% (146/729) and 37.4% (752/2012) with a

cut-o of ≤40 or ≤50 years, respectively. Besides non-BRCA1/2 risk genes

which may associate with early onset OC, it was recently suggested that

constitutive BRCA1 promoter hypermethylation, measurable in blood-de-

rived DNA, may be an OC risk factor.

Methods: We analysed a clinical sample of 455 gBRCA1/2 mutation-neg-

ative OC patients with early onset (≤40 years) for germline mutations

in additional established OC risk genes (BRIP1, RAD51C/D, MSH2/6)

and quantied BRCA1 promoter methylation in blood-derived DNA in

423 of these patients and an additional 476 female cancer-free control

individuals.

Result: Pathogenic germline mutations in the additional OC risk genes

were identied in ve of the 455 patients only (1.1%, 1 BRIP1, 1 MSH2,

1 MSH6, 2 RAD51C). e quantitative methylation analysis revealed

BRCA1 promoter hypermethylation (≥5% cut-o) in 26 of the 423 OC

patients examined (6.1%) which was signicantly higher than in controls

(7/476, 1.5%, OR: 4.39, 95%CI: 1.79-11.22, P=0.00025). Results remain

signicant with a ≥2% cut-o (36/423 cases vs. 20/476 controls; OR: 2.12,

P=0.008). e age at onset was 30.5 years (range 14-40) in OC patients

with ≥5% BRCA1 promoter hypermethylation vs. 31.1 years (range 18-40)

without.

Discussion: Our results support the hypothesis that BRCA1 hypermeth-

ylation represents an OC risk factor, though further analyses are required.

Conclusion: Further studies are ongoing in our laboratory to investi-

gate whether BRCA1 hypermethylation in blood correlates with BRCA1

hypermethylation in the corresponding tumour samples.

Disclosure Statement: e authors declare no conict of interest.

674

Ecacy of niraparib by timing of surgery and residual disease:

a post-hoc analysis of patients in the PRIMA/ENGOT-OV26/

GOG-3012 study

Roisin O’cearbhaill1; Jacek Grabowski2; Jose-Alejandro Pérez-Fidalgo3;

Bradley J Monk4; Ignacio Tusquets5; Colleen Mccormick6; Jose Fuentes

Pradera7; Richard. G. Moore8; Christof Vulsteke9,10; Mark Shahin11; Frederic

Forget12; William H. Bradley13; Sakari Hietanen14; David O’malley15; Anne

Dørumn16; Brian M. Slomovitz17; Klaus Baumann18; Frédéric Selle19; Paula

M. Calvert20; Grazia Artioli21; Tally Levy22; Aalok Kumar23; Izabela

Malinowska24; Yong LI24; Divya Gupta24; Antonio González-Martín25

1GOG and the Department of Medicine, Memorial Sloan Kettering Cancer

Center, Weill Cornell Medical College, New York, USA

2Department of Gynecology, Campus Virchow Clinic, Charité Comprehensive

Cancer Center (CCCC), Charité Medical University Berlin, Berlin, Deutschland

3INCLIVA University Hospital of Valencia, CIBERONC, Department of Medical

Oncology, Valencia, Spanien

4University of Arizona College of Medicine, Creighton University School of

Medicine , Arizona Oncology (US Oncology Network), Phoenix, USA

5Hospital del Mar, Medical Oncology Department, Barcelona, Spanien

6GOG and Legacy Medical Group Gynecologic Oncology, Portland, USA

7Hospital de Valme, Servicio de Oncologia, Sevilla, Spanien

8Division of Gynecologic Oncology, Wilmot Cancer Institute, Department of

Obstetrics and Gynecology, University of Rochester, Rochester, USA

9BGOG and the Department of Medical Oncology and Hematology, AZ Maria

Middelares, Ghent, Belgien

10Antwerp University, Center for Oncological Research, Department of Molecular

Imaging, Pathology, Radiotherapy and Oncology, Antwerp, Belgien

11Abington Hospital-Jeerson Health, Sidney Kimmel Cancer Center of Thomas

Jeerson University, Willow Grove, USA

12Libramont Hospital, Department of Medical Oncology, Libramont, Belgien

13GOG and the Department of Obstetrics and Gynecology, Medical College of

Wisconsin, Milwaukee, USA

14Turku University Hospital, Department of Obstetrics and Gynecology, Turku,

Finnland

15James Comprehensive Cancer Center, Ohio State University, Columbus, USA

16The Norwegian Radiumhospital, Oslo University Hospital, Gynecologic

Oncology, Oslo, Norwegen

17Broward Health, Florida International University Wertheim College of

Medicine, USA

18Arbeitsgemeinschaft Gynäkologische Onkologie and the Department of

Gynecology and Obstetrics, Klinikum der Stadt Ludwigshafen, Ludwigshafen,

Deutschland

19GINECO and Groupe Hospitalier Diaconesses-Croix Saint Simon, Paris,

Frankreich

20Cancer Trials Ireland, Dublin, Irland

21ULSS 3 Serenissima, U.O.C. Oncologia ed Ematologia Oncologica, Venice,

Italien

22Sackler School of Medicine, Tel Aviv University, Wolfson Medical Center,

Department of Obstetrics and Gynecology, Holon, Israel

23Fraser Valley Cancer Centre, BC Cancer, Department of Medical Oncology,

Surrey, Kanada

24GlaxoSmithKline, Waltham, USA

25Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Medical

Oncology Department, Clínica Universidad de Navarra, Madrid, Spanien

Background: Niraparib is approved as maintenance treatment for

patients (pts) with newly diagnosed advanced/recurrent ovarian, pri-

mary peritoneal, or fallopian tube cancer (OC) aer response to plati-

num-based chemotherapy (CT). e PRIMA/ENGOT-OV26/GOG-3012

(NCT02655016) study showed that niraparib following rst-line (1L)

treatment improved progression-free survival (PFS) in the overall inten-

tion-to-treat (ITT) population (hazard ratio [HR] 0.62; 95% CI 0.50–0.76).

Methods: is double-blind, placebo (PBO)-controlled, phase 3 trial eval-

uated niraparib in pts with newly diagnosed, advanced, high-grade serous

or endometrioid OC with a complete or partial response to 1L CT. Pts

were considered to be at high risk for disease progression based on their

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 121

clinical characteristics. is post-hoc analysis presents niraparib ecacy

(PFS) by time of surgery and residual disease status, and was not powered

to determine dierences among subgroups.

Result: Data cuto was May 2019. In total, 733 pts were randomized in

PRIMA. Pts who underwent primary debulking surgery (PDS; n=236) or

interval debulking surgery with neoadjuvant CT (IDS, n=481) had simi-

lar ecacy with niraparib maintenance treatment versus PBO in the ITT

population (PFS HRs [95% CI] were 0.67 [0.468–0.964] and 0.57 [0.441–

0.731], respectively). Niraparib treatment reduced risk of progression

by 42% (95% CI 0.391–0.864) in pts who received PDS and had visible

residual disease (VRD, n=183), 35% (95% CI 0.461–0.91) in those with

IDS and no visible residual disease (NVRD, n=304), and 59% (95% CI

0.269–0.620) in those with IDS and VRD (n=149). Ecacy was not evalu-

able for pts with PDS and NVRD due to low sample size (n=37).

Discussion: In this post-hoc analysis, the impact of residual disease aer

PDS or IDS on the ecacy of niraparib was comparable across subgroups.

Pts with IDS and VRD had the highest reduction in the risk of progression.

Conclusion: ese results suggest timing of surgery does not impact

niraparib ecacy.

Previously presented at SGO 2021; reused with permission.

Funding: GSK 213359.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

764

QuantiGene-Molecular Proling Histology assay shows

superior accuracy in cervical dysplasia detection by

multiplexed Human Papillomavirus oncogene and cellular

biomarker expression quantitation

Nicole Schaefer1; Gunther Schauberger2; Anna Sophie Skof1;

Stefanie Klug2; Andreas Kaufmann1

1Clinic for Gynecology, Charité-Universitätsmedizin Berlin, HPV Laboratory,

Berlin, Deutschland

2Department of Sport and Health Sciences, Technical University of Munich,

Epidemiology, München, Deutschland

Background: Cervical dysplasia are caused by HPV and accompanied by

cellular biomarker upregulation. Screening programs switch from cytol-

ogy to HPV testing. While HPV tests have a higher sensitivity (95% vs.

50%), the specicity is low (<40%). Expression quantitation of cellular

progression-associated biomarkers may enhance specicity and diag-

nosis of dysplastic stages. QuantiGene-Molecular Proling Histology

(QG-MPH) assay enables ecient multiplexed HPV oncogene and bio-

marker mRNA detection and quantitation.

Methods: e QG-MPH assay was designed, individually quantifying

E7 oncogene mRNA of 18 high-risk HPVs, cellular housekeeping genes,

and 10 established biomarkers in a multiplexed format. On a referral

population logistic regression and ROC-analyses were performed and

risk scores with related cut-o values were calculated for disease stages

CIN2+, CIN3+, and CxCa. A nested sample set (550 patients) of a popula-

tion-based cohort (MARZY study, Mainz, Germany) was reanalysed. e

risk score results were compared to standard of care screening methods

(PAP, LBC, HC2, GP5+/6+-PCR) and four dierent co-testing variants

(PAP+HC2, PAP+PCR, LBC+HC2, LBC+PCR). Histological endpoints

CIN2+ and CIN3+ were evaluated.

Result: 61 women (all peculiar plus 5% randomly selected healthy con-

trols) had a histology endpoint. Nine CIN2+ and six CIN3+ were histo-

logically conrmed. Sensitivity and specicity for detection by QG-MPH

risk scores was 67% and 83% for CIN2+, and 83% and 82% for CIN3+,

respectively. Cytology was less sensitive (PAP: 33%; LBC: 33%) and simi-

larly specic (PAP: 79%; LBC: 89%) for the detection of CIN3+. e HPV

tests and the four co-testing strategies had similar sensitivities (83%) but

lower specicities (range 26-67%).

Discussion/Conclusion: Due to equal sensitivity but signicantly higher

specicity compared to all HPV- and co-testing approaches to detect

CIN3+, the QG-MPH assay presents a potentially superior method for

cervical cancer screening. ese data warrant further assay evaluation in

larger prospective screening cohorts.

Disclosure Statement: e authors declare the following: Patent, Honorae,

Beratergremien

776

Monocentric evaluation of radio(chemo)therapy [R(C)T]

forvulval squamous cell carcinoma (VSCC)

Jacqueline Possiel; Katja Döring Laura Anna Fischer;

Markus Anton Schirmer; Manuel Guhlich; Andrea Hille;

Stefan Rieken; Leif Hendrik Dröge; Sandra Donath; Martin Leu

Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,

Göttingen, Deutschland

Background: Radical vulvectomy is the standard of care for VSCC.

Denitive R(C)T plays a crucial role as alternative treatment in patients

(pat) with inoperable VSCC. To date, hardly any prospective study has

evaluated the outcome of those pat.

Methods: We retrospectively analyzed 57 pat ≥18 years without distant

metastasis that received radiotherapy at our hospital. Patient and tumor

characteristics, comorbidities as well as acute and late toxicities were

analyzed. e primary endpoints were 5-year overall (OS) and progres-

sion-free survival (PFS), locoregional (LRC) and distant (DC) control.

As statistical methods we used univariable cox-regression and log-rank

statistics.

Results: Median pat age was 74 years (28.0-90.0 years). Median follow-up

was 18 months (2.0-187.0). 36 patients underwent resection of vulval car-

cinoma followed by postoperative R(C)T. 21 pat received denitive R(C)T.

23/57 pat. were treated with concomitant chemotherapy. IMRT was used

in 18/57 pat. 5-year OS was 60.6%, PFS 46.5%, LRC 55.9% and DC 95.0%.

Normofractionated external beam radiotherapy was administered at a

median total dose of 50.4 Gy (36.0-76.4 Gy). III° side eects were observed

in 15/57, mostly skin reactions (n=15). Patients with multimodal therapy

(surgery + R(C)T) had a signicant better OS (HR 0.19, CI 0.07-0.50,

p<0.01), PFS (HR 0.29, 95% CI 0.13-0.63, p<0.01) and LRC (HR 0.21,

95% CI 0.07-0.61, p<0.01). Additionally, patients with acute toxicities ≥

III° presented a worse OS (HR 3.15, 95% CI 1.24-8.01, p=0.02).

Discussion: is retrospective study shows that R(C)T is generally well

tolerated in pat treated for VSCC and might be considered for pat not suit-

able for surgery, although OS, PFS and LRC are worse. erefore, patient

selection should be evaluated by experienced radiation oncologists and

surgeons based on the patient´s general condition, tumor category and

comorbidities.

Conclusion: R(C)T for the treatment of VSCC is a safe therapy option

with acceptable toxicity.

Disclosure Statement: e authors declare no conict of interest.

828

Combined expression of the progesterone receptor A/RIP140

is a negative independent prognosticator for cervical cancer

Fabian Garrido1; Mathis Wild1; Udo Jeschke1; Christian Dannecker1;

Franziska Dobler1; Bernd Kost2; Sven Mahner2; Helene Heidegger2;

Doris Mayr3; Vincent Cavailles4; Aurelia Vattai2

1University Hospital Augsburg, Department of Obstetrics and Gynecology,

Augsburg, Deutschland

2LMU Munich, University Hospital, Department of Obstetrics and Gynecology,

Munich, Deutschland

3LMU Munich, Department of Pathology, Munich, Deutschland

4Université Montpellier, Institut de Recherche en Cancérologie de Montpellier

(IRCM), INSERM U1194 , Montpellier, Frankreich

Purpose: e role of the progesterone receptor A (PR-A) for cervical

cancer outcome is ambivalent. In mouse models it seems to play a rather

protective role for cancer development. In many other tumor types, PR-A

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts122

expression corresponds to favorable outcome. RIP140 on the other hand,

was already identied as a negative prognostic factor for survival of cer-

vical cancer patients. e aim of this study was to assess the prognostic

value of PR-A in cervical cancer tissue samples and to correlate the results

with clinicopathological parameters.

Methods: In 250 cervical cancer patients, the expression of PR-A was

evaluated by immunohistochemistry. Prognosis determining aspects were

calculated by uni- and multivariate analysis.

Results: Correlation analysis revealed a trend association with RIP140,

HPV virus protein E6, a negative correlation with p16 and a positive

correlation with EP3. PR-A expression was positively correlated with

International Federation of Gynecology and Obstetrics (FIGO) classi-

cation and PR-A was signicantly higher expressed in adeno carcinomas

compared to squamous epithelial carcinoma subtypes. Univariate sur-

vival analyses revealed PR-A as a negative prognosticator for survival.

Multivariate analyses showed that the combined expression of both PR-A

and RIP140 is an independent marker for survival of cervical cancer

patients.

Conclusion: erefore PR-A has to be considered as a negative factor for

cervical cancer survival.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1015

Preoperative conization of early cervical carcinoma associated

with improved progression free survival, a retrospective

single center analysis

Laura Delebinski1; Hermann Hertel1; Peter Hillemanns1; Rüdiger Klapdor1

1Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und

Geburtshilfe, Hannover, Deutschland

Background: e purpose of this study was to examine the association of

patient characteristics and surgical interventions with the progression free

survival and overall survival in patients with cervical carcinoma.

Methods: In total 276 patients with cervical carcinoma through FIGO

IB1 were included in this singlecenter study. In this retrospective analysis,

multivariate cox regression was performed by adjusting for age, lymph

node status, tumor diameter, grading, preoperative conization, adjuvant

therapy and surgical approach (abdominal, laparoscopic).

Result: For 52,5% of the patients the minimally invasive approach and for

44,9% the open abdominal approach was chosen, respectively. e sur-

gical approach was neither a predictive marker for overall survival (OR

1,220; 95% KI: 0,460 – 3,236; p=0,689) nor for progression free survival

(OR 1,295; 95% KI: 0,548 – 3,06; p=0,556) in our study. However, a preop-

erative conization was the only variable strongly associated with improved

survival (OR 4,022; 95% KI: 1,243 – 13,012; p=0,020).

Discussion: In 114 patients with macroscopically complete tumor resec-

tion by conization 8 recurrences occurred. is could be a surrogate for

the prognostic role of tumor cell contamination during laparoscopic hys-

terectomy in patients with macroscopic tumor.

Conclusion: Patients with preoperative conization represent a low risk

collective that might still prot from laparoscopic hysterectomy. Further

prospective, randomized studies on minimally invasive surgery for cervi-

cal cancer must include techniques to prevent intraoperative tumor cell

contamination.

Disclosure Statement: e authors declare no conict of interest.

1050

The Comparative Clinical Eectiveness of Dostarlimab

(dostar) Versus Doxorubicin (dox) in the Treatment (tx) of

Advanced/Recurrent Endometrial Cancer (A/R EC)

Theresa Link1; Cara Matthews2; Domenica Lorusso3,4; Robert L. Coleman5;

Daniel Parks6; Susan Boklage6; Jamie Garside7

1Department of Gynecology and Obstetrics, Technische Universität Dresden,

Dresden, Deutschland

2Brown University, Providence, USA

3Fondazione Policlinico Gemelli of Rome, Rom, Italien

4Department of Gynecologic Oncology, Catholic University of Sacred Heart,

Rom, Italien

5Texas Oncology, US Oncology Research, Dallas, USA

6GlaxoSmithKline, Upper Providence, Collegeville, USA

7GlaxoSmithKline, London, Vereinigtes Königreich

Background: Dostar is approved for patients (pts) with A/R mismatch

repair decient/microsatellite instability high (dMMR/MSI-H) EC. Its

ecacy was evaluated in the single arm GARNET trial (NCT02715284).

Systematic literature review identied the dox control arm of the ZoptEC

trial (NCT01767155) for indirect tx comparison vs GARNET using

pt-level data.

Methods: GARNET Cohort A1 (dMMR/MSI-H A/R EC) and ZoptEC

dox (A/R EC) pts were matched by eligibility criteria. A sensitivity anal-

ysis included all pts who received study drug in both arms. For overall

survival (OS) in months, a Cox proportional hazards model with inverse

probability of tx weighting (IPTW) was used. Kaplan–Meier analysis was

used for progression-free survival (PFS), duration of response (DoR) and

time to deterioration (TTD) in quality of life (QoL), in months. Overall

response rate (ORR) and safety were summarized descriptively. 95% con-

dence intervals (CIs) were estimated with the Clopper–Pearson method.

Result: Median (m) OS (95% CI) was longer for dostar (n=92) vs dox

(n=233) (NR [18.0–NR] vs 11.2 [10.0–13.1]; hazard ratio [HR] 0.41

[95% CI 0.28–0.61; p<0.0001]). Sensitivity analysis (dostar n=129; dox

n=249) gave similar HR (0.40; 95% CI 0.28–0.58). mPFS (95% CI) was

8.1 (3.2–NR) for dostar vs 4.9 (4.1–6.6) for dox. ORR (95% CI) was 43.5%

(33.2–54.2) for dostar vs 13.7% (9.6–18.8) for dox; mDoR was NR vs 8.4,

respectively. mTTD in QoL (95% CI) was 7.1 (2.8–NR) for dostar (n=62)

and 4.5 (4.1–5.4) for dox (n=188). % of pts with adverse events (AEs) lead-

ing to tx discontinuation (12% vs 15%) and serious AEs (34% vs 30%) were

similar. Grade ≥3 AEs were lower for dostarlimab vs dox (48% vs78%).

Discussion: -

Conclusion: Improved OS was observed with dostar in pts with dMMR/

MSI-H A/R EC vs dox in A/R EC. Safety proles were consistent with

prior studies. is suggests dostar has a favorable benet:risk ratio in

thesepts.

Indication of source: GSK 215333. Data under license from Aeterna Zentaris.

Previously presented at SGO 2022; Phoenix, AZ (#216); presented on behalf of

original authors with permission.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 123

1055

Antitumor activity and safety of dostarlimab therapy in

patients (pts) with endometrial cancer (EC) by age subgroups:

a post-hoc analysis from the GARNET trial

Lars Hanker1; Ana Oaknin2; Lucy Gilbert3; Anna Tinker4; Renaud Sabatier5;

Jubilee Brown6; Cara Matthews7; Valentina Boni8; Vanessa Samouelian9;

David O’malley10; Andrea Jewell11; Susana Banerjee12; Grace Antony13;

Jennifer Veneris14; Bhavana Pothuri15

1Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland

2Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO),

Barcelona, Spanien

3Division of Gynecologic Oncology, McGill University Health Centre, Montreal,

Quebec, Kanada

4BC Cancer–Vancouver, Vancouver, British Columbia, Kanada

5Department of Medical Oncology, Institute Paoli-Calmettes, Marseille,

Frankreich

6Division of Gynecologic Oncology, Levine Cancer Institute, Atrium Health,

Charlotte, NC, USA

7Brown University, Providence, RI, USA

8START Madrid CIOCC (Centro Integral Oncológico Clara Campal), Hospital

Universitario HM Sanchinarro, Madrid, Spanien

9Gynecologic Oncology Service, Department of Obstetrics and Gynecology,

Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Kanada

10The Ohio State University College of Medicine, Columbus, OH, USA

11University of Kansas Medical Center, Kansas City, KS, USA

12The Royal Marsden NHS Foundation Trust and Institute of Cancer Research,

London, Vereinigtes Königreich

13GlaxoSmithKline, London, Vereinigtes Königreich

14GlaxoSmithKline, Waltham, MA, USA

15Gynecologic Oncology Group (GOG) and Department of Obstetrics/

Gynecology, Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA

Background: Median age of EC diagnosis is 62 y, yet most EC deaths

occur in pts >65 y (median 70 y). Unmet need in older pts is not addressed

by current standard of care. Dostarlimab is an anti-programmed death

receptor 1 (PD-1) antibody. We report a post-hoc analysis of dostarlimab

antitumor activity and safety by age in pts with dMMR/microsatellite

instability high (MSI-H) EC and MMR procient (MMRp)/MS stable

(MSS) EC.

Methods: GARNET (NCT02715284) is a Phase I, single-arm study of

dostarlimab in pts with advanced/recurrent (A/R) solid tumors. Pts with

dMMR/MSI-H EC were enrolled in Cohort A1 and pts with MMRp/MSS

EC in Cohort A2. Pts were stratied: <65 y, ≥65 to <75 y, or ≥75 y at base-

line. Antitumor activity and safety were assessed. Data cut was March 1,

2020.

Result: In Cohort A1 (n=129), 51.2% of pts were <65 y, 39.5% were ≥65

to <75 y, and 9.3% were ≥75 y. In Cohort A2 (n=161), 43.5% were <65 y,

44.7% were ≥65 to <75 y, and 11.8% were ≥75 y. In the ecacy-evaluable

population (measurable disease at baseline; ≥24 w follow up), objective

response rates (ORRs) (95% condence interval [CI]) per RECIST v1.1

assessed by BICR were similar across age groups for pts with dMMR/

MSI-H EC (<65 y: 45.3% [31.6–59.6] vs ≥65 to <75 y: 43.9% [28.5–60.3] vs

≥75 y: 45.5% [16.7–76.6]) and for pts with MMRp/MSS EC (<65 y: 9.1%

[3.4–18.7] vs ≥65 to <75 y: 16.9% [9.0–27.7] vs ≥75 y: 21.1% [6.1–45.6]).

ere were few Grade ≥3 treatment-related adverse events (TRAEs) (for

pts with dMMR/MSI-H EC [n=129]: 13.6% vs 13.7% vs 8.3%, respec-

tively) and for MMRp/MSS EC [n=161]: 22.9% vs 19.4% vs 5.3%, respec-

tively); observed TRAEs were similar between groups.

Conclusion: Dostarlimab antitumor activity and safety for pts with

dMMR/MSI-H EC and MMRp/MSS EC were comparable across age

groups, with low Grade ≥3 TRAE incidence. Older pts with A/R dMMR/

MSI-H EC experienced broadly similar treatment benets as younger pts.

Indication of source: GSK 213346. Previously presented at SGO, Phoenix, AZ;

Mar 18–21 2022 (abstract #210) and presented at DKK 2022 on behalf of original

authors with their permission.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts124

Head and Neck Cancer

Best-of-Abstract-Vortrag

HANNA: Eectiveness and quality-of-life data from a

real-world study of patients (pts) with recurrent and/or

metastatic squamous cell carcinoma of the head and neck

(R/M SCCHN) treated with nivolumab (NIVO) in Germany

Harald Müller-Huesmann1; Eyck von der Heyde2; Dennis Hahn3;

Christine Langer4; Boris Kubuschok5; Ulrike Bockmühl6; Gunter Klautke7;

Paul-Stefan Mauz8; Bernd Reuter9; Dirk Beutner10; Jens Büntzel11;

Jens von der Grün12; Chia-Jung Busch13; Bálint Tamaskovics14;

Jorge Riera-Knorrenschild15; Kerstin Gutsche16; Manfred Welslau17;

Thomas Gauler18; Daniela Waldenberger19; Andreas Dietz20

1Brüderkrankenhaus St. Josef Paderborn, Paderborn, Deutschland

2Onkologische Praxis am Raschplatz, Hannover, Deutschland

3Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Deutschland

4Universitätsklinikum Gießen und Marburg, Gießen, Deutschland

5Universitätsklinikum Augsburg, Augsburg, Deutschland

6Klinikum Kassel, Kassel, Deutschland

7Klinikum Chemnitz gGmbH, Chemnitz, Deutschland

8Universitätsklinikum Tübingen, Klinik für Hals-, Nasen- und Ohrenheilkunde,

Tübingen, Deutschland

9SRH Zentralklinikum Suhl GmbH, Suhl, Deutschland

10Universitätsmedizin Göttingen, Klinik und Poliklinik für Hals-Nasen-

Ohrenheilkunde, Göttingen, Deutschland

11Südharz Klinikum Nordhausen gGmbH, Nordhausen, Deutschland

12Universitätsklinikum Frankfurt, Klinik für Strahlentherapie, Frankfurt,

Deutschland

13Universitätsmedizin Greifswald, Klinik und Poliklinik für Hals-, Nasen- und

Ohrenheilkunde, Greifswald, Deutschland

14Universitätsklinikum Düsseldorf, Klinik für Strahlentherapie und

Radioonkologie, Düsseldorf, Deutschland

15Philipps-Universität Marburg, Marburg, Deutschland

16Carl-Thiem-Klinikum Cottbus gGmbH, Cottbus, Deutschland

17Klinikum Aschaenburg, Hämato-Onkologische Schwerpunktpraxis,

Aschaenburg, Deutschland

18Universitätsklinikum Essen, Klinik für Strahlentherapie, Essen, Deutschland

19Bristol Myers Squibb, München, Deutschland

20Universitätsklinikum Leipzig, Klinik und Poliklinik für Hals-, Nasen-,

Ohrenheilkunde, Leipzig, Deutschland

Background: HANNA (NCT03114163) is a prospective, multicenter

study in Germany that collects real-world data from pts with R/M

SCCHN treated with NIVO aer platinum (pt)-based therapy. Overall,

487 adult pts with R/M SCCHN were enrolled and treated according to

the NIVO label.

Methods: is interim analysis represents data from 477 analyzable pts

enrolled until Jul 2021. e primary study objective is overall survival

(OS, estimated using the Kaplan-Meier method). Secondary study objec-

tives include duration of treatment (DOT), safety, patient-reported out-

comes (PROs) and quality of life (QoL) measured with FACT-H&N, and

EQ-5D questionnaires. All data were analyzed in a descriptive manner.

Result: Median follow-up was 32.9 mo. Median age was 64 (range 30–86)

years. Most pts were men (81.1%), and most pts (74.2%) had a history

of smoking. ECOG PS was 0/1/2/3 in 14.0/44.9/24.7/5.9% of pts, respec-

tively. e locations of the primary tumor were oropharynx, 37.7%; oral

cavity, 22.2%; hypopharynx, 19.1%; larynx, 14.7%; and others, 6.3%.

47.2% of pts received NIVO as rst-line (1L) therapy for R/M SCCHN

aer pt-based therapy, 43.8% in 2L, and 9.0% in third/later lines (3+L).

Median OS (mOS) was 10.9 mo. Former/current smoking did not impair

mOS (10.9 mo for current/former smokers vs 10.4 mo for non-smokers,

P=0.8932). mOS was 20.2, 11.0, and 6.1 mo for pts with ECOG PS 0,1, and

2+, respectively. e overall median DOT (mDOT) was 5.4 mo. mDOT

was 5.7 mo for 1L, and 5.3 mo for 2L and 4,6 mo for 3L. For pts with

ECOG PS 0, 1, 2, and 3, mDOT was 8.8, 5.3, 3.3, and 1.9 mo, respectively.

Grade 3/4 treatment-related or immune-related adverse events were

observed in 11,9% of all pts. QoL measured with FACT-H&N remained

stable until mo 24 overall and in all subscale scores. PROs measured with

EQ-5D reected similar outcomes.

Discussion & Conclusion: Real-world data from HANNA show that

NIVO is eective in a broad patient population. e treatment is well tol-

erated and the PRO/QoL remained stable under therapy.1

Source:

1. Previously presented at ESMO 2021, FPN 924P, H. Müller-Huesmann et al.

Reused with permission.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

566

Eag1 Potassium Channel in Oral Squamous Cell Carcinoma – a

proof of principle study

Susanne Wolfer1; Luis Pardo2; Philipp Kaumann1; Boris Schminke1;

Tobias Bürger3; Henning Schliephake1

1Universitätsmedizin, MKG, Göttingen, Deutschland

2Max-Planck-Institut für Experimentelle Medizin, Göttingen, Deutschland

3Universitätsmedizin, Pathologie, Göttingen, Deutschland

Background: Eag1 was among the rst voltage-gated potassium-channels

associated with oncogenesis and tumor development (1). Its expression

prole makes it an interesting new target for tumor therapy (2). Eag1 was

found in many types of tumors, but there were only few studies for head

and neck carcinomas and especially for oral squamous cell carcinoma

(OSCC). is study aimed to screen for Eag1 in OSCC and to correlate its

expression with clinical parameters.

Methods: In this study, OSCC tissue samples were investigated by immu-

nouorescence. Patient-matched normal oral mucosa was used as control.

e expression results were compared to the clinical data. Descriptive sta-

tistics were performed and disease-free-survival was calculated using the

Kaplan-Meier method.

Result: All controls were Eag1 negative. 33 of 46 tumor samples (71.7%)

were positive for Eag1; 14 of them (30.4%) strongly positive. ere was

no correlation to T- or N-stage but bad prognostic factors were more fre-

quent in with Eag1 positive cases (p=0.0017), which showed more recur-

rence (p=0.0059). Two-thirds (76.9%; 10/13) Eag1-negative tumors had

no recurrence event so far. e disease-free-survival was signicantly

shorter in the 14 Eag1 strong positive tumors (p=0.0382). e overall-sur-

vival is also clearly reduced in the strongly positive cases (p=0.0232).

Discussion: A relationship between Eag1 and advanced stages und poorly

dierentiated carcinomas was already known, for larynx and pharynx

(3). We observe similar association on OSCC, but this study is the rst

one to show a signicant association between Eag1 expression and tumor

recurrence.

Conclusion: OSCC shows Eag1 expression that appears to correlate with

prognosis. Investigations with larger sample sizes are necessary to further

conrm these results and clarify the prognostic inuence.

References:

1 Comes N et al. (2015) Biochim Biophys Acta 1848 (2015) 2477–2492

2 Hemmerlein B et al. (2006) Mol Cancer 2006, 5:41

3 Menéndez ST et al. (2012) J Mol Med 2012 90:1173–1184.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 125

Poster

125 years of radiotherapy: Could organ sparing radiotherapy

for larynx cancer have prevented World War I?

Thomas Brunner1; Herbert Wördeho1; Ahmed Gawish1; Uwe Busch2

1Universtiätsmedizin Magdeburg, Klinik für Strahlentherapie, Magdeburg,

Deutschland

2German Roentgen Museum, Remscheid, Deutschland

Background: Shortly aer the discovery of x-rays in 1895 curative

organ-sparing radiotherapy (RT) of larynx cancer (LXC) was introduced.

e death of the German Emperor Frederick III (FIII) from untreated

LXC resulted in William II (WII) as his successor on the throne who his-

torically is regarded to be responsible to have led Europe into World War

I (WWI).

Methods: Analysis of historical sources to recapitulate the development

of curative RT for LXC and descriptions of FIII’s LXC and of his treat-

ment were put into political context with a special focus on the escalation

towards WWI, and the role of Emperor WII who succeeded to the crown.

Pertinent historical illustrations of technical developments of RT were

summarized in a video.

Result: e rst reported treatment of head and neck cancer with RT

dates back to February 3, 1896 by Voigt in Hamburg, and Dobson in

London specically described treatment of the larynx in 1901. Both, tele-

therapy and brachytherapy techniques, were developed and rened in

the 20s by Regaud in Paris. FIII’s glottic LXC measured 2 x 4 mm at its

rst description. Queen Victoria’s son-in-law was treated by German and

English physicians but denite pathological diagnosis was delayed by a

year resulting in cT4 cN1 disease incompatible with cure, and leading to

his death on 15 June 1888. is was eight years before the rst RT of a head

and neck tumour. Nevertheless, FIII could have been cured by voice pre-

serving RT had it been introduced a few years earlier. e hopes were high

that FIII would lead Germany towards a more liberal course reected in

the thoughts of Nietzsche who saw the early death of FIII as a crucial and

decisive tragedy for Germany. FIII was succeeded by WII who led a more

militaristic and expansionistic political regime which probably aected all

of Europe.

Discussion: RT of LXC started strinkingly early aer the discovery of

x-rays and radioactivity shortly aer FIII’s death from a potentially cur-

able LXC.

Conclusion: Organ sparing RT for LXC is a prime example of compatibil-

ity of curative therapy with quality of life.

Disclosure Statement: e authors declare no conict of interest.

111

Radiotherapy or chemoradiation for head and neck tumors - a

cohort of younger patients

Christoph Süß1; Elena Nickel1; Tobias Ettl2; Felix Steger1; Katja Evert3;

OliverKölbl1; Matthias Hautmann1

1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,

Regensburg, Deutschland

2Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,

Universitätsklinikum Regensburg, Regensburg, Deutschland

3Institut für Pathologie, Universitätsklinikum Regensburg, Regensburg,

Deutschland

Background: Radiotherapy and chemoradiation (R(C)T) are well-estab-

lished treatments of locally advanced head and neck carcinoma (HNC).

However, few data exist regarding collectives with patients younger than

40 years. e aim of the present study was to collect and evaluate clinical

parameters, feasibility and outcomes of RCT in a cohort of young patients

with HNC.

Methods: From 2002 to 2019, 78 patients aged 40 years or younger were

included. e collective of 21 women and 57 men had a median age of

38 years at diagnosis, 50 patients suered from HNC UICC stage IVa. 31

patients underwent denitive R(C)T. 47 received resection followed by

adjuvant R(C)T. Simultaneous RCT was performed in 53 patients. Median

follow-up was 21 months (mo) (IQR 10 - 62).

Result: RT was performed as planned in 69% of cases. Interruption of RT

for two or more days occurred in 14 (31%) of 78 patients. In 5 patients,

therapy was discontinued prematurely for various reasons. Of 53 RCT-

treated patients, 32 (60.4%) received a dose > 75% of the initially pre-

scribed chemotherapy. Any acute toxicity ≥ CTC grade III occurred in

32.1% of patients. Twelve weeks aer completion of R(C)T, 57 patients

(73.1%) were free of cancer, and 5 (6.4%) were in partial remission. Overall

survival (OS) was 84% aer 12 mo, 65% aer 24 mo, and 57% aer 60 mo.

Progression-free survival (PFS) of treated patients was 90% aer 12 mo,

79% aer 24 mo and 68% aer 60 mo.

e risk of relapse was signicantly associated with non-HPV-induced

tumors and non-in-sano resection.

Discussion: Regarding side eects and the still improvable prognosis,

currently discussed de-escalation strategies should be evaluated carefully,

especially due to the young age. For patients with high risk for relapse also

an escalation of therapy might be discussed.

Conclusion: Compared to patient cohorts without age selection, young

patients have a better OS and PFS aer 5 years. A multimodal therapy

concept should be aimed at in a collective of younger patients.

Disclosure Statement: e authors declare no conict of interest.

Indication of source:

1 https://doi.org/10.1007/s00066-020-01620-0

131

Methylation and expression signatures of surgical margins in

comparison to tumor and healthy tissue

Tsima Abou Kors1; Jasmin Ezić1,2; Ole Ammerpohl3; Julian Benckendor4;

Thomas F.E. Barth4; Martin Bens5; Jaya Thomas6; Johann M. Kraus7;

Johannes Doescher1; Adrian von Witzleben1; Marie-Nicole Theodoraki1;

Cornelia Brunner1; Jens Greve1; Patrick Schuler1; Thomas K. Homann1;

Christian Ottensmeier6,8; Hans A. Kestler7; Simon Laban1

1Ulm University Medical Center, Department of Otorhinolaryngology and Head

& Neck Surgery, Ulm, Deutschland

2SVA System Vertrieb Alexander GmbH, Wiesbaden, Deutschland

3Ulm University and Ulm University Medical Center, Institute for Human

Genetics, Ulm, Deutschland

4Ulm University Medical Center, Institute of Pathology, Ulm, Deutschland

5Fritz Lipmann Institute, Leibniz Institute on Aging, Jena, Deutschland

6University of Southampton - Faculty of Medicine, Cancer Sciences Unit,

Southampton, Vereinigtes Königreich

7Ulm University and Ulm University Medical Center, Institute of Medical Systems

Biology, Ulm, Deutschland

8University of Liverpool - Faculty of Medicine, Institute of Systems, Molecular

and Integrative Biology - Liverpool Head and Neck Center, Liverpool, Vereinigtes

Königreich

Background: Human papillomavirus (HPV) positive and HPV-negative

oropharyngeal squamous cell carcinoma (OPSCC) (HPV-) dier prog-

nostically and on a molecular level. Traditionally, surgical margins

are assessed patho-histologically, primarily utilizing light-microscopy.

Molecular changes in the tumor bed may predate microscopically detect-

able changes and could result in locoregional recurrence. We aimed to

compare DNA methylation and RNA expression in the primary tumor,

the tumor-free resection margin, and healthy mucosa obtained from

OPSCC patients.

Methods: Aer informed consent, snap-frozen tissue samples of the

tumor, resection margin, and healthy mucosa from 29 OPSCC patients

were obtained intraoperatively. Total RNA and DNA were extracted using

AllPrep DNA/RNA Mini Kit (Qiagen, Germany). DNA methylation

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts126

proling was performed using Innium Methylation EPIC 850K, and

RNA sequencing was performed using Illumina HiSeq2500 (16 tumors)

and Illumina NovaSeq 6000 (rest). Data analysis was performed in R

(4.0.2).

Result: All margin samples were taken from clear resection margin tissue

(R0) with a mean distance of 9mm to the tumor. Exploratory and unsu-

pervised hierarchical clustering analysis conrmed an aggregation based

on tissue type irrespective of HPV status. Signicant dierences in DNA

methylation and gene expression between OPSCC tumor, resection mar-

gin, and healthy mucosa samples were detected.

Discussion: Resection margin data displayed distinct signatures converg-

ing minimally with tumor while intersecting heavily with healthy tissue

signatures.

Conclusion: is project continues establishing methylation and expres-

sion signatures for OPSCC tumor, margin, and healthy mucosa using

Nanopore sequencing.

Disclosure Statement:

Simon Laban: Advisory Boards: Merck Sharp & Dohme (MSD), Bristol Myers

Squibb (BMS), Astra Zeneca (AZ), Sano Genzyme. Honoraria: MSD, BMS,

Merck Serono.

143

Impact of standard therapy on immune checkpoint regulation

in 2D and 3D HNSCC models

Annette Aolter1; Kai Liebel1; Elena Seiz1; Alexya Azhakesan1;

Anne Lammert1; Sonja Ludwig1; Karen Bieback2; Johann Kern1;

Nicole Rotter1

1Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie,

Universitätsmedizin Mannheim, Mannheim, Deutschland

2Institut für Transfusionsmedizin und Immunologie, Universitätsmedizin

Mannheim, DRK-Blutspendedienst Baden-Württemberg – Hessen

gemeinnützige GmbH, Mannheim, Deutschland

Background: e inhibition of immunoregulatory checkpoints such as

the PD-1 / PD-L1 axis is one of the most important immunotherapeutic

strategies for head and neck squamous cell carcinomas (HNSCC). Despite

encouraging results of clinical trials, immunotherapeutic approaches fre-

quently fail to control the tumor disease in patients. Clinical trials evaluat-

ing the combination of immune checkpoint inhibitors (ICI) with already

established therapies are ongoing, but the inuence of these conventional

treatments on immune checkpoint regulation remains elusive.

Methods: Irradiation (IR) alone and in combination with cisplatin or

cetuximab was applied to a HNSCC 2D cell culture model. IR was adapted

to fractionated clinical application schemes. e impact of these standard

treatment pillars on the expression of PD-L1 and signaling pathways

involved in resistance development were assessed by Western Blot, CFA,

and IHC. Results were validated in an ex vivo 3D HNSCC tissue culture

model additionally treated with ICI to consider the therapeutic response

of the tumor microenvironment, particularly immune cells.

Result: A profound induction of PD-L1 by cisplatin was observed in vitro.

Combining IR with cisplatin exerted even stronger eects. Compared to

single IR dosages, the expression of resistance-mediating MAP-Kinase

phospho-ERK1/2 was upregulated aer fractionated IR. Heterogeneity in

PD-L1 expression and ERK phosphorylation was also reected in the ex

vivo model.

Discussion: We provide experimental evidence for an impact of stan-

dard radiochemotherapy on PD-L1 expression in HNSCC. Adaptation of

MAPK to a fractionated IR scheme could indicate a resistance mechanism

to prolonged radiotherapy. e ex vivo culture technology might oer a

promising tool for individualized drug ecacy testing.

Conclusion: Our ndings suggest a complex and probably context-de-

pendent PD-L1 regulation upon application of radiochemotherapy and

further experimental and (pre-)clinical analyses will be essential to

unravel underlying molecular principles.

Disclosure Statement: e authors declare no conict of interest.

146

Volume reduction of salivary glands under Radio(chemo)

therapy (R(C)T) for head and neck tumors

Julia Dressler1; Matthias Hautmann1; Felix Steger1; Manuel März1;

Christian Gröger1; Oliver Kölbl1; Christoph Süß1

1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,

Regensburg, Deutschland

Background: RT and RCT are important treatment options for head and

neck carcinoma (HNC). However, xerostomia is a frequent side eect.

e aim of this retrospective study was to evaluate salivary gland volumes

under/aer R(C)T.

Methods: 44 patients with HNC treated with RT or RCT at UKR between

2011 and 2015 were included. Median age was 62.5 years with 7.3%

female and 92.7% male patients. 11 patients obtained adjuvant treatment,

33 received primary R(C)T. 31 patients had concurrent RCT, while 13

received RT alone.

In all 44 patients, salivary gland volumes (Gll. parotideae and submandib-

ulares) were determined separately before start of RT, within 6 weeks aer

RT, and at follow-up periods (3,6, and 12 months aer RT) by volumetric

evaluation of imaging (CT and/or MRI).

Result: Volumes of salivary glands were signicantly smaller aer RT than

before RT at all times examined. Volumes of Gll. parotideae (mean -35%,

p < 0.0001) and Gll. submandibulares (-18%, p < 0.05) showed signi-

cant reduction within 6 weeks aer RT compared to volumes before RT.

Neither Gll parotis nor Gll submandibulares increased in volume within

12, 24 (n=9), nor 36 (n=3) months (p-values: 0.6 - 0.8).

Parotid glands showed no more signicant volume change over time more

than 12 months aer RT. Submandibular glands volumes were signi-

cantly lower aer 12 months compared to volumes aer 6 months post

RT. ere was a correlation between volume change of salivary glands and

mean dose arrived.

Discussion: Volumes of parotid and submandibular glands were signi-

cantly lower aer RT than before. Even up to 3 years aer therapy, salivary

gland volumes do no more increase signicantly. ese results are consis-

tent with correlation of xerostomia in patients aer RT.

Conclusion: e eects of RT on gland volumes result in changes of

patient anatomy that could be optimized during the course of therapy

by adaptive radiation planning. us, it would be possible to potentially

reduce the toxicity of therapy.

Disclosure Statement: e authors declare no conict of interest.

Indication of source:

1 https://doi.org/10.1007/s00066-021-01791-4

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 127

228

Challenges in recruiting of head and neck cancer patients to

participate in home exercise study

Sabine Felser1; Christian Junghanß1; Julia Rogahn1;

Daniel Fabian Strueder2; Brigitte Kragl1; Sabina Ulbricht3;

Christina Große-Thie1; East German Study Group of Hematology and

Oncology (Osho)4

1Rostock University Medical Center, Department of Medicine Clinic III,

Hematology, Oncology, Palliative Medicine, Rostock, Deutschland

2Rostock University Medical Center, Department of Otorhinolaryngology, Head

and Neck Surgery, Rostock, Deutschland

3Institute for Community Medicine, University Medicine Greifswald, Department

of Social Medicine and Prevention, Greifswald, Deutschland

4Ostdeutsche Studiengruppe Hämatologie und Onkologie e. V., Leipzig,

Deutschland

Background: Physical activity interventions are reported to bear con-

siderable benet for head and neck cancer patients (HNSCC pts). Some

studies have shown that HNSCC pts prefer exercise at home, alone and

with moderate intensity. To address this preferences we conceived a holis-

tic exercise program and evaluated the concept in a pilot study regarding

its feasibility and achieved eects1. In an ongoing multicenter study, this

exercise program is evaluated into a home based setting²,³. Preliminary

data show that the recruitment of 60 HNSCC pts is challenging. Herein

we analyzed characteristics of those consenting or not consenting to par-

ticipate in the study.

Methods: Direct response of HNSCC pts in tumor aercare consultation

including recording of interest in participation or reasons for refusal.

Result: Of 134 HNSCC pts surveyed (82% male), 12 expressed interest

(9%). Of these, eight (6%) consented to participate. ree additional

pts were included via a self-aid group. Of the currently included 11 pts

55% are female. e average age is 71 ± 7 years. Seven (64%) HNSCC pts

have a (technical) high school diploma. By self-report, seven (64%), are

non-smokers, three (27%) are ex-smokers, and one (9%) is a smoker. Nine

of 11 were active in sports before the disease. e main reasons for refusal

were “independently active” (N = 47), “no complaints” (N = 31), and “no

interest” (N = 23).

Conclusion: In sum, the recruitment rate is low. e HNSCC pts recruited

do not reect the typical HNSCC pts (male, smoker, lower educational

level). erefore, consideration should be given to using monetary incen-

tives to increase the motivation to participate.

Indication of source:

1 Felser S et al., Integrative cancer therapies 2020; 19: 1-12

2 Felser S et al., ONCOLOGY RESEARCH AND TREATMENT 2020; 43 (SUP-

PL 4): 134

3 DRKS-ID: DRKS00023883

Disclosure Statement: e authors declare no conict of interest.

262

Postoperative adjuvant radiochemotherapy (aRCH) with

cisplatin versus aRCH with cisplatin and pembrolizumab

in locally advanced head and neck squamous cell carcinoma -

the ADRISK trial

Susanne Wiegand1; Gunnar Wichmann1; Peter Brossart2; Holger Kaftan3;

Marc Münter4; Victor Lewitzki5; Nicole Rotter6; Georg Maschmeyer7;

Carmen Stromberger8; Thomas Gauler9; Ursula Schröder10;

Matthias Hautmann11; Martin Görner12; Orlando Guntinas-Lichius13;

Gunnar Hapke14; Bálint Tamaskovics15; Steen Dommerich16;

Anett Schmiedeknecht17; Andreas Dietz1

1Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde, Universitätsklinikum

Leipzig, Leipzig, Deutschland

2Med. Klinik IIII/ZIM, Hämatologie/Onkologie, Universitätsklinikum Bonn, Bonn,

Deutschland

3Klinik für Hals-Nasen-Ohrenheilkunde, Helios Klinikum Erfurt GmbH, Erfurt,

Deutshcland

4Klinik für Radioonkologie und Strahlentherapie, Klinikum Stuttgart -

Katharinenhospital, Stuttgart, Deutschland

5Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Würzburg,

Würzburg, Deutschland

6Hals-Nasen-Ohrenklinik, Universitätsklinikum Mannheim, Mannheim,

Deutschland

7Klinik für Hämatologie, Onkologie und Palliativmedizin, Ernst-von-Bergmann

Klinikum Potsdam, Potsdam, Deutschland

8Klinik für Radioonkologie und Strahlentherapie, Charite - Universitätsmedizin

Berlin, Berlin, Deutschland

9Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen,

Deutschland

10Klinik für Hals-, Nasen- und Ohrenheilkunde Campus Lübeck,

Universitätsklinikum Schleswig-Holstein, Lübeck, Deutschland

11Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,

Regensburg, Deutschland

12Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum Bielefeld,

Bielefeld, Deutschland

13Klinik für Hals-Nasen-Ohrenheilkunde, Universitätsklinikum Jena, Jena,

Deutschland

14Onkologisches Zentrum, Kath. Marienkrankenhaus gGmbH, Hamburg,

Deutschland

15Klinik für Strahlentherapie und Radiologische Onkologie, Universitätsklinikum

Düsseldorf, Düsseldorf, Deutschland

16Klinik für Hals-Nasen-Ohrenheilkunde, Charite - Universitätsmedizin Berlin,

Berlin, Deutschland

17Zentrum für Klinische Studien Leipzig, Medizinische Fakultät, Universität

Leipzig, Leipzig, Deutschland

Background: PD-1immune checkpoint inhibitors have been approved

as therapy in head and neck squamous cell carcinoma (HNSCC) as they

demonstrated a gain in overall survival (OS) in recurrent/metastatic dis-

ease. e next step is to explore the ecacy of immune checkpoint inhib-

itors in the curative setting. e aim is to describe herein the design and

rationale of the ADRISK trial, a prospective, multicenter, randomized

controlled phase II trial within the German Interdisciplinary Study Group

of German Cancer Society (IAG-KHT) of addition of pembrolizumab

to standard postoperative adjuvant cisplatin-based radiochemotherapy

(aRCH) in the treatment of patients with locally advanced intermediate-

and high-risk HNSCC.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts128

Methods: Patients with primary resectable stage III and IV HNSCC of

the oral cavity, oropharynx, hypopharynx and larynx with pathologic high

(R1, extracapsular nodal extension) and intermediate risk (R0 <5mm;

N≥2) aer surgery who are eligible for cisplatin-based aRCH aer surgery

will receive either standard aRCH with cisplatin versus the same treat-

ment + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months). e

objectives are to show that addition of pembrolizumab to cisplatin-based

aRCH improves event-free survival and OS compared with aRCH alone

in locally advanced intermediate and high-risk HNSCC. ADRISK will

recruit 240patients with advanced HNSCC in 16 centers to provide a pre-

cise survival estimate aer 24 months. Recruitment started in August 2018

and is ongoing (Trial registration: NCT03480672). Until March 2022, 158

patients were registered for the trial and 152 patients were randomized.

Discussion: Given the unmet need for reducing high rates of relapse in

intermediate-to-high-risk HNSCC patients by improved adjuvant treat-

ment, it is expected that ADRISK will provide new insights into treatment

in this setting and might demonstrate the ability of pembrolizumab to

improve survival of this patient group.

Disclosure Statement: e authors declare the following: wissenschaliche

Präsentationen, Mitarbeit in advisory Boards und Forschungsunterstützung durch

verschiedene Pharmarmen

352

Distress (DT) Monitoring in Head and Neck Cancer patients.

A feasibility study during surgical treatment

Sebastian Hoefert1; Annika Emmler1; Norbert Schäeler2; Siegmar Reinert1

1Universitätsklinikum Tübingen, Klinik- und Poliklinik für Mund-, Kiefer- und

Gesichtschirurgie, Tübingen, Deutschland

2Universitätsklinikum Tübingen, Psychosomatische Medizin und

Psychotherapie, Innere Medizin VI, Tübingen, Deutschland

Background: Certied Head and Neck Cancer Centres in Germany sup-

port patients with psychooncology. Usually, a distress (DT) assessment is

performed at the time of admission prior to therapy and psychooncology

support is provided at patients´ request.

Aim of this study was to measure DT at point of admission, before sur-

gery, aer surgery (end of intensive care unit) and before discharge to

analyse DT continuously.

Methods: Prior to surgical cancer therapy, psychooncological screening

is performed using the Tablet PC method. e test includes the NCCN

Distress ermometer (DT) and was measured again before surgery, aer

surgery, and before discharge to analyze the feasibility of DT measure-

ments and potential time points with high DT impact.

Result: A total of 49 patients were studied, 43% of whom were male. At

discharge, DT was minimally reduced in contrast to admission (1 point;

median). Patients with psycho-oncological support showed no signicant

dierence, except shortly aer surgery with reduced DT values in contrast

to patients without psychooncological support. DT measurement was

found to be helpful by most patients´ berits.

Discussion: Our study showed no signicant dierences in DT levels

during surgical treatment. In patients with psycho-oncological support,

there were no signicant dierences at the time of discharge, but signi-

cantly lower DT levels shortly aer surgery (end of ICU).

Conclusion: Our initial results demonstrate the feasibility of continuous

DT measurement and high stability of DT levels during surgical treatment.

Disclosure Statement: e authors declare no conict of interest.

430

Comparison between dierent lymph node predictors for

head and neck cancer: a population-based analysis of the

Thuringian cancer registries in Germany in 2009 and 2010

Mussab Kouka1; Elisa Al Ahmar1; Jens Büntzel2; Holger Kaftan3;

Daniel Böger4; Andreas Müller5; Stefan Schultze-Mosgau6; Thomas Ernst7;

Orlando Guntinas-Lichius1

1Universitätsklinikum Jena, Klinik für Hals-, Nasen- und Ohrenheilkunde, Jena,

Deutschland

2Südharzklinikum, Klinik für Hals-, Nasen- und Ohrenheilkunde, Nordhausen,

Deutschland

3Helios Klinikum Erfurt, Klinik für Hals-Nasen-und Ohrenheilkunde, Erfurt,

Deutschland

4SRH Zentralklinikum Suhl, Klinik für Hals-, Nasen- und Ohrenheilkunde, Suhl,

Deutschland

5SRH Wald-Klinikum Gera, Klinik für Hals-, Nasen- und Ohrenheilkunde , Gera,

Deutschland

6Universitätsklinikum Jena, Klinik für Mund-, Kiefer- und Gesichtschirurgie/

Plastische Chirurgie, Jena, Deutschland

7Universitätsklinikum Jena, Klinik für Innere Medizin II, Hämatologie und

Internistische Onkologie, Jena, Deutschland

Background: e aim of this population-based study was to compare and

evaluate the impact of dierent lymph node (LN) classication systems on

overall survival (OS) from head and neck cancer (HNC).

Methods: In this retrospective cohort study, data of all 401 patients

(median age: 57 years; 80% male, 47% stage IV) were included who were

diagnosed with HNC in 2009 and 2010 and were treated with neck dis-

section (ND) in uringian hospitals due to this diagnosis. Total num-

ber of lymph nodes removed (TNOD), number of positive lymph nodes

(PNOD), lymph node ratio (LNR) and log odds of positive lymph nodes

(LODDS) were comparatively analyzed regarding to OS.

Result: e average for the follow-up was 48 ± 32.1 months. e

average number of TNOD and PNOD in a unilateral ND were

13.6 ± 10.4 and 1.4 ± 2.7, respectively. e average number of

LNR and LODDS were 0.16 ± 0.27 and -0.96 ± 0.57, respectively.

In the multivariable analysis risk factors age > 57 years [hazard ratio (HR)

2.21; p = 0.007] and an advanced pT4 tumor stage [HR 3.38; 95% con-

dence interval (CI) 1.027 - 11.112; p = 0.045] were signicant. At the high-

est tumor stage, UICC stage IV, there was an increased risk of death [HR

9.218; 95% CI 2.721 - 31.224; p < 0.001]. PNOD as well as LNR showed no

independent inuence on OS while LODDS > -1.0 proved to be a signi-

cant independent predictor for OS with a 2.12-fold increased risk of death

[HR 2.120; 95% CI 1.129 - 3.982; p = 0.019].

Discussion: Recent studies have investigated the impact of LODDS on

HNC tumors in a single-institution study. In this study, LODDS was supe-

rior over the commonly used classication LNR and PNOD in a multi-in-

stitution analysis covering an entire federal state in Germany. Several

authors have set the LODDS cuto values very subjectively. A standard-

ization of the LODDS cuto values and a larger patient population in a

multinational clinical study are needed to conrm and validate our results.

Conclusion: In comparison to existing lymph node classication LODDS

was the best and independent node prognosticator for OS in HNC in a

real-world setting.

Disclosure Statement: e authors declare no conict of interest.

432

Exosomal serum biomarkers as predictors for laryngeal

carcinoma

Sarina Müller; Johannes Schuster; Olaf Wendler; Heinrich Iro;

Antoniu-Oreste Gostian

Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Deutschland

Background: Laryngeal carcinomas are the third most common head and

neck cancer. Whereas glottic carcinomas present themselves relatively

early with voice changes, especially localizations in the supra- and sub-

glottic regions lead to locally advances carcinomas at the time of diagnosis

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 129

in about 40% of the cases. Currently, there is no screening method and

diagnosis is dicult and can only be made by laryngoscopy. us, the

objective of this study was to identify exosomal serum biomarkers that

can diagnose laryngeal carcinomas and distinguish between early and late

stages.

Methods: IRB approved single center study of n=14 patients with laryn-

geal carcinomas (Stage I, Stage IV) and n=7 controls who all underwent

a panendoscopy for tumor staging and biopsy. A multiplexed proteomic

array (n=2000 proteins) on exosomes isolated from serum collected at the

day before surgery was performed. e most promising proteins for diag-

nosis and dierentiation were calculated using biostatistical methods and

were validated using Western Blots and Immunohistochemistry.

Results: TIE-1 (fold change (FC) 6.3) was the best protein to distinguish

between any stage of laryngeal carcinoma and control patients. PKLR (FC

10.2) was the most underexpressed protein in Stage IV compared to Stage

I whereas SOX 17 (FC 9.2) was the most overexpressed.

Discussion: All identied proteins have not been described before and

represent potentially novel biomarkers. However, those results have to be

validated in a second independent and larger cohort. Exosomal biomark-

ers show a superior signal-to-noise-ratio compared to whole serum and

therefore may be an important tool for non-invasive biomarker proling

for laryngeal carcinoma in the future.

Conclusions: TIE-1, PKLR and SOX17 have been identied as potential

novel biomarkers for the diagnosis of laryngeal carcinoma as well as dif-

ferentiation between dierent stages. Further studies are needed to vali-

date these results.

Disclosure Statement: e authors declare no conict of interest.

445

OncSaliva – a feasibility study with promising epigenetic

biomarkers for improved detection of head and neck cancer in

non-invasive specimen

Anna-Bawany Hums1; Carolin Dippmann1; Anne Hennig1; Lars Jansen2;

Matthias Dürst2; Martina Schmitz1; Alfred Hansel1; Orlando Guntinas-

Lichius3; Juliane Priese3

1oncgnostics GmbH, Jena, Deutschland

2Universitätsklinikum Jena, Klinik für Gynäkologie, Jena, Deutschland

3Universitätsklinikum Jena, Klinik für Hals-Nasen- und Ohrenheilkunde, Jena,

Deutschland

Background: Head and neck squamous cell carcinoma (HNSCC) are

mainly diagnosed at advanced tumor stage aer the onset of symptoms.

Timely detection would improve the options for successful treatment. We

identied and validated ve epigenetic markers in comparative studies

using primary HNSCC and healthy tissue. Aim of the current non-inter-

ventional OncSaliva study is to establish diagnostics of HNSCC including

saliva, swabs and tissue. Tumor marker detection is further monitored in

saliva and swabs postsurgery.

Methods: Five DNA methylation markers and a bisulte-specic ref-

erence were analyzed using fresh-frozen tissue, saliva or swabs from

HNSCC patients and controls. Samples were bisulte-converted before

use in methylation-specic multiplex QPCR. e goal is to include 100

controls and 100 HNSCC patients, the latter with 2-year follow-up exam-

ination until end of 2023.

Result: Until now 25 HNSCC and 7 control patients were included in the

study. e tumor marker ZNF671 was sensitively detected in HNSCC

tissue (21 samples positive) and associated saliva samples (19 samples

positive). One saliva sample was detected positive in the control group

for ZNF671, so far. Concordant results for ZNF671 (positive or nega-

tive) between both specimen from a single patient occurred in 17/25 for

HNSCC and 6/7 within controls. Swab examinations results are not yet

available. Data from individual patient follow-ups will be presented at the

congress.

Conclusion: Preliminary results from recent patient samples support our

study hypothesis to robustly detect HNSCC markers in both, tissue and

saliva. Utilization of saliva samples for cancer-specic diagnostic assays

based on epigenetic markers will be useful in in vitro diagnostics aiming

at secondary and tertiary prevention.

Disclosure Statement: e authors declare no conict of interest.

453

Therapy in HNC patients and nutrition – a patient centered

study

Andreas Cofre1; Stefanie Walter2; Jutta Huebner1; Jens Büntzel3

1Univrsitätsklinikum Jena, Hämatologie und internistische Onkologie, Jena,

Deutschland

2Bundesverband der Kehlkopfoperierten e.V., Bonn, Deutschland

3Südharzklinikum Nordhausen, Klinik für HNO Erkrankungen, HNO, Nordhausen,

Deutschland

Background: Most patients with head and neck cancers (HNC) are mal-

nourished, before diagnosis, due to the stomatognathic system being dis-

turbed at its onset. is paper questions how our patients experience their

treatment, the aermath and nutrition as a whole.

Methods: To formulate essential issues with nutrition aer HNC- treat-

ment we performed narrative interviews with members of the Federal

Association of Laryngectomy Patients and developed a questionnaire

comprising of 47 questions. We asked for, demographic data, weight his-

tory and side eects and oered multiple choice, visual scales, and free

text in a patient friendly way. It was handed to support groups and tumor

aercare patients for an intern validation and used statistical methods

such as the χ2-, sher- and the one way- Anova test.

Result e return rate was n=154 of which 36 identied as female and 88

as male. and had a median age of 65.5 years (39-86). e average time aer

treatment was 5.3 years (0.1-31).

We compared 3 endpoints with baseline weight: overall patients lost 7.8

% bodyweight aer the operation, 12.7% aer radio-chemotherapy and

gained 0.1% aer convalescence. Patients above 100 kg starting weight are

more likely to experience malnutrition while ending up with 17 % less

bodyweight aer convalescence (p<0.0001)

We asked for side eects like loss of smell (55.4%), dry mouth (56.3%),

dysphagia (57.1% ) and dental problems (33%) of which some were related

to a specic treatment (radiation and xerostomia) others reinforce each

other (xerostomia and dental problems). e analysis suggests a gradual

increase in adverse eects with the number of interventions performed.

For patients with only radiotherapy or surgery this dierence was signif-

icant (p < 0.0001).

Conclusion: Our patient centered data shows the correlation between

performed treatments and weight and therefore nourishment. In the sub-

group analysis, particularly heavier patients are at risk of malnutrition,

and we could show that more therapy also means more side eects.

Disclosure Statement: no conict of interest.

454

The impact of peritherapeutic antibiotics administration on the

oncological outcomes of head-and-neck squamous cell carcinoma

patients undergoing radiotherapy

Jiadai Zou1,2; Ilinca Popp1,2; Margaretha Glaser1; Lennard Halle1;

Andreas Knopf2,3; Anca-L. Grosu1,2; Nils Henrik Nicolay1,2;

Alexander Rühle1,2

1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im

Breisgau, Deutschland

2Deutsches Konsortium für Translationale Krebsforschung (DKTK),

Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Deutschland

3Klinik für Hals-, Nasen- und Ohrenheilkunde, Universitätsklinikum Freiburg,

Freiburg im Breisgau, Deutschland

Background: Antibiotics administration can worsen the prognosis of

cancer patients receiving immune checkpoint inhibitors, potentially by

inuencing patients’ microbiome-immune system axis. We aimed to

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts130

evaluate the eects of antibiotic administration on the oncological out-

comes of head-and-neck squamous cell carcinoma (HNSCC) patients

receiving denitive (chemo)radiotherapy [(C)RT].

Methods: In a single-center analysis, 220 HNSCC patients who were

treated with (C)RT between 2010 and 2019 were analyzed, and infor-

mation about antibiotic application including indication, duration and

classes were taken from electronic patient records. Using t-tests and chi-

square tests, patient characteristics were compared depending on antibi-

otics usage. e impact of antibiotic prescription on the progression-free

(PFS) and overall survival (OS) was examined using Kaplan-Meier and

Cox analyses.

Result: 154 patients (70%) received antibiotics in a time interval ranging

between 30 days before (C)RT until completion of (C)RT. e median

duration of antibiotic application was 3 days (range, 1-49 days). While

93 (42%) patients obtained antibiotics during the 30 days prior to (C)RT,

100 (46%) were treated with antibiotics during (C)RT. e most common

indication was single-shot antibiotic prophylaxis prior to port catheter

implantation (n=132). ECOG status, age and radiotherapy dose did not

dier in patients treated with antibiotics. Peritherapeutic antibiotics use

deteriorated PFS (median 10 vs. 24 months, p<0.05, HR=1.40) and OS

(median 26 vs. 36 months, p<0.05, HR=1.41), while pretherapeutic usage

did not. In patients aged ≤75 years, antibiotic prescription during (C)RT

remained an independent variable for reduced PFS and OS in the multi-

variate Cox analysis.

Discussion: Prospective trials including microbiome analyses are required

to better understand the mechanisms behind the observed eects of anti-

biotics in HNSCC patients.

Conclusion: Peri- but not pretherapeutic antibiotics usage was associated

with reduced outcomes of HNSCC patients undergoing (C)RT.

Disclosure Statement: e authors declare no conict of interest.

458

Dysregulation of immune checkpoint molecules in oral cancer

Manuel Weber1; Rainer Lutz1; Jacek Glajzer1; Jan-Erik Werry1;

Christoph Baran1; Gesche Frohwitter1; Markus Eckstein2; Marco Kesting1;

Jutta Ries1

1Mund-, Kiefer- und Gesichtschirurgische Klinik Erlangen, Erlangen, Deutschland

2Pathologisches Institut, Erlangen, Deutschland

Background: An involvement of immune cell inltration and immune

regulation for the progression of oral squamous cell carcinomas (oscc)

is shown. Anti-PD1 therapy is approved for treatment of advanced oscc

cases and currently investigated for neoadjuvant use prior to denitive

surgery. e number of identied ccellular receptors with immune check-

point function is constantly increasing. A comparing analysis of a large

number of immune checkpoints in oscc is missing.

Methods: A Nano-String mRNA analysis was performed to assess the

expression of 21 immuno-regulatory checpoint molecules in 98 oscc

tumor samples and 41 healthy oral mucosa specimens.

Result: In oscc a signicantly increased expression of CD115, CD163,

CD68, CD86, CD96, GITRL and PD-L1 was detected. Additionally,

a marginally signicant increased CD8 expression was observed. e

expression of CD137L was signicantly downregulated in oscc compared

to healthy oral mucosa.

Discussion: Upregulation of the inhibitory CD96 receptor and PD-L1

ligand as well as the activating CD137L ligand could contribute to reduced

eector T-cell function and local immunosuppression in oscc. Increased

expression of the activating CD86 and GITRL could be explained by an

increased inltration of myeloid cells (CD115, CD68, CD163) and T-cells

(CD8) in oscc tissue.

Conclusion: e analysis contributes to the understanding of immune

escape in oscc and reveals potential targets for oral cancer immunotherapy.

Disclosure Statement: e authors declare no conict of interest.

476

Updated analysis of the phase II CheckRad-CD8 trial: First-line

treatment of locally advanced head and neck squamous cell

carcinoma with induction chemoimmunotherapy followed by

radioimmunotherapy

Markus Hecht1; Markus Eckstein2; Annett Kallies1; Jens von der Grün3;

Thomas Illmer4; Gunther Klautke5; Simon Laban6; Matthias Hautmann7;

Thomas Brunner8; Bálint Tamaskovics9; Axel Hinke10; Jian-Guo Zhou1;

Benjamin Frey1; Anna-Jasmina Donaubauer1; Ina Becker1; Sabine

Semrau1; Arndt Hartmann2; Panagiotis Balermpas3; Wilfried Budach9;

UdoGaipl1; Heinrich Iro11; Antoniu-Oreste Gostian11; Rainer Fietkau1

1Friedrich-Alexander-Universität Erlangen-Nürnberg,Strahlenklinik, Erlangen,

Deutschland

2Friedrich-Alexander-Universität Erlangen-Nürnberg, Pathologie

3Goethe-Universität Frankfurt am Main, Strahlentherapie, Frankfurt am Main,

Deutschland

4Gemeinschaftspraxis Hämatologie Onkologie, Arnoldstraße, Dresden, Dresden,

Deutschland

5Klinikum Chemnitz, Strahlentherapie, Chemnitz, Deutschland

6Universitätsklinikum Ulm, Hals-Nasen-Ohrenheilkunde, Ulm, Deutschland

7Universitätsklinikum Regensburg, Strahlentherapie, Regensburg, Deutschland

8Otto-von-Guericke-Universität Magdeburg, Strahlentherapie, Magdeburg,

Deutschland

9Heinrich-Heine-Universität Düsseldorf, Strahlentherapie, Düsseldorf,

Deutschland

10Clinical Cancer Research Consulting (CCRC), Düsseldorf, Deutschland

11Friedrich-Alexander-Universität Erlangen-Nürnberg, Hals-Nasen-

Ohrenheilkunde, Erlangen, Deutschland

Background: e trial studied induction chemoimmunotherapy followed

by radioimmunotherapy with double checkpoint inhibition aer CD8+

immune cell based patient selection.

Methods: Patients with stage III-IVB HNSCC were enrolled in this mul-

ticenter phase II trial. Study treatment consisted of a single cycle of cispla-

tin 30mg/m² d1-3, docetaxel 75mg/m² d1, durvalumab 1500mg x dose

d5 and tremelimumab 75mg x dose d5. Patients with increased intra-

tumoral CD8+ immune cell density or pathological complete response

(pCR) in the re-biopsy entered radioimmunotherapy up to a total dose

of 70Gy. Patients received further three cycles of durvalumab/tremelim-

umab followed by eight cycles of durvalumab mono (q4w). is updated

analysis was performed with data-cut o on June 7th 2021 (data-cuto for

rst analysis was January 17th 2021, presented at ASCO2021).

Result: Between September 2018 and May 2020, 80 patients were enrolled.

Median follow up was 17.2 months. Aer pathological patient selection,

60 patients entered radioimmunotherapy. In comparison to the rst anal-

ysis, the radioimmunotherapy cohort maintained a high progression-free

survival rate at one and two years of 78% and 72%, respectively, and an

overall survival rate at one and two years of 90% and 84%, respectively.

Furthermore, the entire cohort maintained a high progression-free sur-

vival rate at one and two years of 75% and 68%, respectively, and an overall

survival rate at one and two years of 87% and 79%, respectively.

Discussion: Induction chemo-immunotherapy followed by chemother-

apy-free radioimmunotherapy aer intratumoral CD8+ immune cell-

based patient selection has promising progression-free survival.

Conclusion: is treatment scheme is worth investigation in future clin-

ical trials.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 131

493

Combining surgery and immunotherapy in the treatment of

head and neck cancer – from neoadjuvant immunotherapy to

salvage surgery

Rainer Lutz1; Tjark-Ole Büntemeyer1; Manuel Olmos1; Jacek Glajzer1;

Jutta Ries1; Marco Kesting1; Manuel Weber1

1Universitätsklinikum Erlangen, Mund-, Kiefer- und Gesichtschirurgische Klinik,

Erlangen,

Background: Immunotherapy (IT) with checkpoint inhibitors is rou-

tinely used in advanced head and neck cancer when surgery and radia-

tion therapy are not available as curative treatment options. e use of IT

has shied to earlier stages in various malignancies. Patients undergoing

IT can potentially have long-term survival, thereby it can be dicult for

oncologic head and neck surgeons to assess the indication for surgery in

these patients.

Methods: We report on four exemplary cases in which surgery and IT

were successfully combined with dierent therapeutic intentions.

Result: In two cases with advanced oral cancer, neoadjuvant IT was per-

formed before surgical tumor resection with curative intent as an “individ-

ual cure attempt”. Currently, both patients are alive and free of recurrence.

In two further cases, local progression occurred during palliative IT.

Tumor resection and microsurgical reconstruction were performed for

local symptom control. Patients survived 7 and 11 months aer surgery

with signicantly improved quality of life.

Discussion: As prospective studies are currently underway, neoadjuvant

IT before surgery may prove to be a valuable treatment for advanced head

and neck cancer with curative intent. Because patients with advanced

tumor disease may have long survival times under IT, palliative surgery

for symptom control should be critically evaluated in patients with pro-

gressive malignant tumors in good general health.

Conclusion: Surgery in combination with immunotherapy can be used as

neoadjuvant therapy in patients with advanced head and neck cancer as

well as to improve the quality of life of palliative patients.

Disclosure Statement: e authors declare no conict of interest.

512

Kinase Inhibitors of DNA-PK, ATM and ATR in Combination

with Ionizing Radiation Can Increase Tumor Cell Death in

HNSCC Cells While Sparing Normal Tissue Cells

Tina Jost1; Eva-Maria Faulhaber1; Julia Symank1; Julian Scheper1;

Felix Bürkel1; Rainer Fietkau1; Markus Hecht2; Luitpold V. Distel3

1Universitätsklinikum Erlangen, Strahlenklinik Erlangen, Strahlenbiologie,

Erlangen, Deutschland

2Universitätsklinikum Erlangen, Strahlenklinik Erlangen, Erlangen, Deutschland

3Universitätsklinikum Erlangen, Strahlenklinik Erlangen, Translationale

Immunonkologie, Erlangen, Deutschland

Background: Kinase inhibitors (KI) targeting components of the DNA

damage repair pathway are a promising new type of drug. Combining

them with ionizing radiation (IR), which is commonly used for treatment

of head and neck tumors, could improve tumor control, but could also

increase undesirable side eects on surrounding normal tissue.

Methods: e eect of KI of the DDR (ATMi: AZD0156; ATRi: VE-822,

dual DNA-PKi/mTORi: CC-115) in combination with IR on HPV-positive

and HPV-negative HNSCC and healthy skin cells was analyzed. Cell death

and cell cycle arrest were investigated using ow cytometry. Additionally,

clonogenic survival and migration behavior were examined.

Result: Studied HNSCC cell lines reacted dierently to DDRi. An increase

in cell death for all of the malignant cells could be observed when com-

bining IR and KI. Healthy broblasts were not aected by simultaneous

treatment. Migration was partially impaired. Inuence on the cell cycle

varied between the cell lines and inhibitors.

Discussion: In conclusion, a combination of DDRi with IR could be feasi-

ble for patients with HNSCC. Side eects on healthy cells are expected to

be limited to normal radiation-induced response. Formation of metastases

could be decreased because cell migration is impaired partially. e treat-

ment outcome for HPV-negative tumors tends to be improved by com-

bined treatment

Conclusion: In conclusion, we found that DDRi in combination with IR

more eectively inhibits tumor growth of HNSCC compared to the single

approaches and, most importantly, has a synergistic eect. e combina-

tion seems not to aect normal tissue surrounding the tumor more than

IR alone. Taken together, combined treatment has the potential to be a

therapeutic option that could improve tumor control without increasing

toxicity.

Reference:

1 Faulhaber, E.-M.; Jost, T.; et al. Kinase Inhibitors of DNA-PK, ATM and ATR

in Combination with Ionizing Radiation Can Increase Tumor Cell Death

in HNSCC Cells While Sparing Normal Tissue Cells. Genes 2021, 12, 925.

https://doi.org/10.3390/genes12060925

Disclosure Statement: e authors declare no conict of interest.

513

The role of plasma interleukin-6 as potential surrogate

parameter for tumor hypoxia in head-and-neck cancer

patients

Alexander Rühle1,2; Jamina T. Fennell1,2; Nicole Wiedenmann1,2;

Birgit Bieber1,2; Michael MIX2,3; Juri Ruf2,3; Raluca Stoian1,2; Dimos Baltas1,2;

Anca-L. Grosu1,2; Nils Henrik Nicolay1,2

1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im

Breisgau, Deutschland

2Deutsches Konsortium für Translationale Krebsforschung (DKTK),

Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Deutschland

3Klinik für Nuklearmedizin, Universitätsklinikum Freiburg, Freiburg im Breisgau,

Deutschland

Background: Tumor hypoxia worsens the prognosis of head-and-neck

squamous cell carcinoma (HNSCC) patients receiving chemoradiation

(CRT). Fluorine-18 misonidazole PET ([18F]FMISO PET) can quantify

tumor hypoxia; however, as the logistic eorts of [18F]FMISO-PET are

considerable, we investigated the role of hypoxia-regulated interleukin-6

(IL-6) as potential surrogate parameter for tumor hypoxia.

Methods: 27 patients receiving denitive CRT within a prospective trial

were included in this analysis. Blood sampling and [18F]FMISO PET

were carried out in weeks 0, 2 and 5 of CRT. IL-6 plasma concentration

was determined using ELISAs. e ratio of tumor [18F]FMISO standard-

ized uptake value (SUV) to mean SUV within the contralateral sterno-

cleidomastoid muscle was calculated and dened as [18F]FMISO SUV

tumor-to-muscle ratio (T/M-ratio). Voxels within the primary tumor and

metastatic lymph nodes that exhibited a T/M-ratio ≥1.4 were summarized

as tumoral hypoxic subvolumes (HSV). e association between IL-6

and HSV was investigated using Pearson’s correlations, and receiver-op-

erating characteristic analyses were conducted regarding the predictive

power of IL-6 for early tumor hypoxia response. e impact of IL-6 on

progression-free (PFS) and overall survival (OS) was investigated with

Cox analyses.

Result: IL-6 strongly correlated with the tumoral HSV at all analyzed

time points (week 0: r=0.775, p<0.001, week 2: r=0.553, p=0.007, week

5: r=0.734, p<0.001). e dierence in IL-6 levels between weeks 0 and 2

signicantly correlated with the tumoral HSV dynamics in this time inter-

val (r=0.533, p=0.011). ROC analyses revealed that IL-6 in week 2 pre-

dicted early tumor hypoxia response (AUC=0.822, p=0.031). Increased

IL-6 levels at week 5 were associated with reduced PFS (p=0.078) and OS

(p=0.013).

Discussion: IL-6 may serve as surrogate parameter for tumor hypoxia

dynamics in HNSCC patients undergoing CRT.

Conclusion: IL-6 plasma levels correlate with tumor hypoxia in HNSCC

patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts132

576

Patient-specic spheroids from squamous cell carcinoma of

the head and neck region (HNSCC) as a tool for personalized

therapy

Anne Lammert; Nicole Rotter; Johann Kern; Annette Aolter;

Sonja Ludwig; Esther Tenschert

Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie,

Universitätsmedizin Mannheim, Mannheim, Deutschland

Purpose: Due to advances in the development of therapy regimes such

as targeted therapies/immunotherapies, cell culture techniques have also

become increasingly important, especially those that grow in 3D archi-

tecture. 3D cell culture models are particularly suitable for evaluating the

response to therapy in vitro, as they represent intercellular signaling mech-

anisms better than 2D cell cultures. Our goal is to develop patient-specic

spheroids that accurately represent the properties of the original tumor

tissue. Based on these, the response to dierent drugs could be evaluated

before use in patients in terms of “personalized medicine”.

Methods: Four HNSCC cell lines (e.g. UMSCC-11A) were used to evalu-

ate optimal culture conditions for spheroid formation in co-culture with

stromal cells. Following tissue samples from HNSCC patients (n=14) were

processed to obtain single cell suspensions. e isolated cells were cul-

tured as spheroid monocultures and co-cultures. Furthermore immuno-

histochemistry (IHC) was performed to evaluate spheroids` expression of

dierent markers of interest (e.g. cancer stem cell markers).

Results: Cell culture protocols developed with the help of cell lines

could also be used for spheroid culture of tumor cells from HNSCC tis-

sue. However, we observed massive dierences between cells from dif-

ferent donors when brought into spheroid culture. Adding stromal cells

increased the reproducibility regarding size and stability of spheroids.

Viability assays showed an over 90% viability aer a week of incubation

and allowed for further testing of spheroids’ cellular structures with IHC

to investigate the arrangement pattern of cell types in comparison to

patients’ tissue.

Conclusions: e method of patient-specic squamous cell carcinoma

spheroids is established in our laboratory. HNSCC is a heterogeneous

entity with a very variable response to therapy. Cell culture models that

accurately represent the architecture of the original tumor are of great

importance on the way to “personalized medicine”.

Disclosure Statement: e authors declare no conict of interest.

646

Co-culture with human mesenchymal stromal cells does

not inuence the in vitro radiosensitivity of head-and-neck

squamous cell carcinoma

Marie Lies1,1,2,2; Maren Strack1,2; Birgit Bieber1,2; Andreas R. Thomsen1,2;

Jochen Hess3,4; Andreas Knopf2,5; Anca-L. Grosu1,2; Nils Henrik Nicolay1,2;

Alexander Rühle1,2

1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im

Breisgau, Deutschland

2Deutsches Konsortium für Translationale Krebsforschung (DKTK),

Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Deutschland

3Arbeitsgruppe Molekulare Grundlagen von HNO-Tumoren, Deutsches

Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland

4Sektion Experimentelle und Translationale Kopf-Hals-Onkologie,

Universitätsklinikum Heidelberg, Heidelberg, Deutschland

5Klinik für Hals-, Nasen- und Ohrenheilkunde, Universitätsklinikum Freiburg,

Freiburg im Breisgau, Deutschland

Background: As mesenchymal stromal cells (MSCs) can aid regener-

ation of radiation-induced normal tissue toxicities, they could serve as

therapeutic agents for the attenuation of radiation-related sequelae in the

head-and-neck region. However, any radioprotective eects of MSCs on

head-and-neck squamous cell carcinoma (HNSCC) should be ruled out

prior to administration of MSC-based therapies.

Methods: Five human papillomavirus (HPV)-negative (UD-SCC5, FaDu,

Cal27, Detroit562, UD-SCC3) and one HPV-positive (UD-SCC2) HNSCC

cell lines were co-cultured with human bone marrow-derived MSCs. A

possible impact of direct and indirect MSC co-culture on the radiosen-

sitivity of HNSCCs was assessed using two- and three-dimensional sur-

vival, proliferation and viability assays. Radiation-induced alterations of

HNSCC cell cycle distribution and apoptosis rates in dependence of MSC

co-culture were examined with ow cytometry, whereas connective tis-

sue growth factor (CTGF) levels were determined using enzyme-linked

immunosorbent assays (ELISA).

Result: ere were no radioprotective eects of direct or indirect MSC

co-culture on HNSCCs in clonogenic survival, proliferation and viability

assays. Irradiation induced a dose-dependent G2/M arrest of HNSCCs at

96h that was not altered by MSC co-culture. Caspase-3 and annexin-V

measurements revealed a dose-dependent increase of radiation-induced

apoptosis in HNSCC samples irrespective of co-cultured MSC. CTGF lev-

els were signicantly increased in direct HNSCC-MSC co-cultures com-

pared to HNSCC mono-cultures, but comparable between the co-cultures

and MSC mono-cultures.

Discussion: ere are inconsistent data whether MSCs could increase

the radioresistance of tumor cells. Our comprehensive approach did not

reveal any radioprotective eects of MSCs on HNSCCs, therefore sup-

porting the usage of MSC-based treatments for the attenuation of radia-

tion-induced toxicities in HNSCC patients.

Conclusion: No radioprotective eects of MSCs on HNSCCs were

detected in a two- and three-dimensional in vitro approach.

Disclosure Statement: e authors declare no conict of interest.

739

Telomere length screening in young patients with head and

neck squamous cell carcinoma is suitable to detect underlying

inherited telomere biology disorders

Mareike Tometten1,2; Benjamin Rolles1,2; Maurice Klein2,3; Mark Ooms2,3;

Philipp Winnand2,3; Eva Simons2,4; Marcel Bourgeois1,2; Gerrit Spanier5;

Simon Laban6; Manuel Weber7; Carolin Goetz8; Falk Birkenfeld9;

Kim Kricheldorf1,2; Susanne Isfort1,2; Martin Kirschner1,2; Stephan

Hackenberg2,4; Frank Hölzle2,3; Fabian Beier1,2; Tim H. Brümmendorf1,2

1University Hospital RWTH Aachen, Department of Hematology, Oncology,

Hemostaseology and Stem Cell Transplantation, Aachen, Deutschland

2Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO-

ABCD), Köln, Deutschland, 3University Hospital RWTH Aachen, Department of

Oral and Maxillofacial Surgery, Aachen, Deutschland

4University Hospital RWTH Aachen, Department of Ear-, Nose- and Throat-

Medicine and Surgery of Head and Neck, Aachen, Deutschland

5University Hospital Regensburg, Department of Cranio-Maxillofacial Surgery,

Regensburg, Deutschland

6University Hospital of Ulm, Department of Ear-, Nose- and Throat-Medicine,

Ulm, Deutschland

7University Hospital of Erlangen, Department of Oral and Maxillofacial Surgery,

Erlangen, Deutschland

8Klinikum rechts der Isar, Technical University Muenchen, Department of Oral

and Maxillofacial Surgery, München, Deutschland

9University Hospital Schleswig-Holstein, Department of Oral and Maxillofacial

Surgery, Kiel, Deutschland

Background: Head and neck squamous cell cancer (HNSCC) aects

mainly males in 6th to 7th decade. Major extrinsic risk factors (RF) are

alcohol, tobacco and HPV-infection. A subset develops HNSCC at young

age <50years (y). Telomere biology disorders (TBD) are characterized by

impaired telomere maintenance and TBD patients (pts) are predisposed

to develop solid cancers arising at early age, amongst which HNSCC

represent the most frequent entity. Premature shortened telomere length

(TL) represents the functional TBD read-out. We systematically analyzed

TL in a young HNSCC pts cohort to identify unknown TBD cases.

Methods: For this sub-cohort, pts <50y at initial HNSCC diagnosis were

eligible. All pts were included in the Aachen telomeropathy registry

(ATR) based on clinical TBD suspicion. Lymphocyte (L) and granulocyte

(G) age-adjusted (aa) TL were analyzed by ow-FISH, next generation

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 133

sequencing (NGS) for telomere maintenance gene mutations performed

when TL found below the 1st percentile.

Result: Six German centers included 40 pts in this ongoing study. Mean

age at initial diagnosis was 42.0 ± 7.2y. Major site was oral tongue. Tumor

stage and RF available in 29 pts showed 18 (62%) with initial stage III or

IV, smoking in 13 (45%), alcohol abuse in six (20%) and 10 (34%) with no

history for both RF. AaTL in L was signicantly lower (-0.59 (p= 0.017))

compared to healthy controls, aaTL in G was normal (0.45 (p= 0,059))

representing premature aging. TL was below the 1st percentile both in L

and G in one patient. NGS screening revealed a homozygous gene muta-

tion suspected to cause TBD.

Discussion: Implementation of routine TL screening for TBD in young

HNSCC pts might improve the management because of expected excess

radiation and/or chemotherapy toxicity. Pre-aged lymphocytes could con-

tribute to tumor development due to chronic inammation or by being

part of a deleterious microenvironment.

Conclusion: TL screening in young HNSCC pts can identify underlying

inherited TBD. Further studies are needed to address the role of prema-

ture TL shortening in this pre-selected group.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Health Economy/Public Health

Best-of-Abstract-Vortrag

415

How the corona pandemic aects cancer patients: Results

from a cross-sectional survey in Germany

Andrea Gaisser1; Rachel Eckford2; Volker Arndt3; Michael Baumann4;

Evelyn Kludt5; Katja Mehlis6; Jasper Ubels2; Eva Winkler6;

Susanne Weg-Remers1; Michael Schlander2

1Krebsinformationsdienst, Deutsches Krebsforschungszentrum, Heidelberg,

Deutschland

2Gesundheitsökonomie, Deutsches Krebsforschungszentrum, Heidelberg,

Deutschland

3Abt. Klinische Epidemiologie, Deutsches Krebsforschungszentrum, Heidelberg,

4Wissenschaftlicher Vorstand, Deutsches Krebsforschungszentrum, Heidelberg,

5Krebsinformationsdienst, Deutsches Krebsforschungszentrum, Heidelberg,

6Klinik für Medizinische Onkologie, Nationales Centrum für Tumorerkrankungen,

Heidelberg, Deutschland

Background: e COVID-19 pandemic required to prioritize health care

services, potentially aecting the care for other vulnerable patients, such

as those with cancer. Beyonduncertaintywith regard to their care and

their risk of infectionpatients mayalso experience psychosocial or other

types of burden. e aim of this pilot survey study is to investigatehow the

pandemic aects medical care of cancer patients and their psychosocial

well-being.

Methods: We surveyed a convenience sample of cancer patients who

contacted the German Cancer Information Service (KID) via e-mail with

questions between July 2020 and June 2021. Using an anonymized online

questionnaire, informationoncancer type and phase, changes incancer

care and pandemic related worries was collected. Anxiety and depression

were assessed using the Hospital Anxiety and Depression Scale (HADS). 

Results: Of 718 responses, 621 were evaluable. Median age of participants

was 60 years, 76.3% were women, and breast cancer was the most fre-

quent cancer type (51.1%). e majority of patients had completed initial

treatment (40%). Overall 12.9% (n=79) of patients reported changes in

their medical care, mostly to follow-up appointments. 33% had consider-

able worries that the pandemic might aect their quality of care, and over

80% missed personal social contacts quite a bit or very much. Near one

h of respondents worried about their jobs and possible nancial losses.

Prevalence of anxiety and depression was 55% and 39%, respectively.

Discussion: Results show that patient well-being and care have been

aected by the corona pandemic.Most patients received their treatment

as planned, but psychological burden in terms of worries, anxiety and

depression was high across the survey period, covering the months aer

wave 1, wave 2 and wave 3.

Conclusion: Our results underscore cancer patients´ psycho-social bur-

den caused by the pandemic. Health care organisationsmust be aware of

this and ascertain equitablecare and services as needed for all patients

particularly in times of crisis.

Disclosure Statement: e authors declare no conict of interest.

1016

Long-term benets, harms and cost-eectiveness of dierent

screening strategies for individuals with familial colorectal

cancer risk in Germany – a decision analysis within the

FARKOR study

Gaby Sroczynski1; Lára R. Hallsson1; Nikolai Mühlberger1; Beate Jahn1,2;

Sabine Homann3; Raphael Rehms3; Doris Lindörfer3; Alexander Crispin3;

Ulrich Mansmann3; Uwe Siebert1,2,4,5

1Institute of Public Health, Medical Decision Making und Health Technology

Assessment, UMIT - University for Health Sciences, Medical Informatics and

Technology, Hall i. T., Österreich

2Division of Health Technology Assessment, ONCOTYROL Center for

Personalized Cancer Medicine, Innsbruck, Österreich

3Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-

Maximilians University, Munich, Österreich

4Center for Health Decision Science, Departments of Epidemiology and Health

Policy & Management, Harvard T. H. Chan School of Public Health, Boston, USA

5Institute for Technology Assessment and Department of Radiology,

Massachusetts General Hospital, Harvard Medical School, Boston, USA

Background: To evaluate the benet-harm balance and cost-eectiveness

of dierent screening strategies using colonoscopy or immunologic fecal

blood testing (iFOBT) in German individuals younger than age 50 with

familial colorectal cancer (CRC) risk.

Methods: A Markov-state-transition model simulating CRC progression

was developed to evaluate various screening strategies diering in screen-

ing test, interval, and age at start and end. We used German clinical, epi-

demiological, and economic data (€2020) along with test accuracy data

from meta-analyses. We adopted the German statutory health insurance

perspective and discounted eects and costs at 3% annually. Evaluated

outcomes included life-years gained (LYG), severe complications (SC)

associated with colonoscopy, incremental harm-benet ratios (IHBR

[SC/LYG]), and incremental cost-eectiveness ratios (ICER [€/LYG]).

Comprehensive sensitivity analyses were performed.

Result: In the base-case analyses (full compliance), IHBRs for iFOBT

screening were 0.00054 (biennial, age 45-65), 0.0014 (biennial, age 35-65),

0.0024 (biennial, age 30-70) and 0.0135 (annual, age 30-54; biennial,

age 55-75) SC/LYG. Corresponding IHBRs for 10-yearly colonoscopy

were 0.001 (age 55-65), 0.004 (age 45-65), 0.006 (age 35-65) and 0.012

(age 30-70) SC/LYG. Compared to standard care, biennial iFOBT age

35-75 was cost-saving. e next more eective iFOBT strategies yielded

ICERs of 2,630 €/LYG (biennial, age 30-70), and 34,675 €/LYG (annual,

age 30-54; biennial, age 55-75), respectively. Compared to standard care,

10-yearly colonoscopy age 45-65 was cost-saving. Moving to earlier start

and later stop yielded ICERs of 2,962, 3,240 and 9,279 €/LYG for 10-yearly

colonoscopy screening at age 40-70, 35-65, and 30-70, respectively.

Conclusion: Oering colonoscopy or iFOBT screening to individuals

younger than age 50 with familial CRC risk can be considered benecial

and cost-eective in the German context. Benet-harm ratios suggest

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts134

10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70

to be acceptable.

Disclosure Statement: e authors declare the following: is work was supported

by GB-A Innovationsfonds Grant: 01NVF17026.

Poster

Urban deprivation and health services uptake: the example of

genetic counselling at the Cologne Centre for Familial Breast

and Ovarian Cancer

Anja Tüchler1, Robert Rémy1, Kerstin Rhiem1, Rita K. Schmutzler1,

Timo-Kolja Pförtner2

1Zentrum Familiärer Brust- und Eierstockkrebs, Uniklinik Köln, Centrum für

integrierte Onkologie (CIO), Köln, Deutschland

2Institut für Medizinsoziologie, Versorgungsforschung und

Rehabilitationswissenschaft, Universität zu Köln, Köln, Deutschland

Background: As the eld of personalized medicine continues to grow,

social inequalities in the use of these health services need to be addressed,

as a social gradient for the utilization of health services has been observed.

We present rst data on socioeconomic dierences in the uptake of genetic

counselling in the German health care setting, using patient data from the

Cologne Centre for Familial Breast and Ovarian Cancer.

Methods: Data from patients with a residential address in Cologne

were assigned to their respective city district (n = 86). Empirical Bayes

Smoothed (EBS) uptake rates per 1.000 inhabitants were calculated for

each district and used as dependent variable in bivariate spatial ordinary

least squares (OLS) regression models. An index for multiple urban depri-

vation for the city of Cologne, migration levels and mean age per city dis-

trict were used as explanatory variables.

Result: Data of 3,109 patients were considered for this analysis. City dis-

trict level EBS-rates ranged from 1.54 – 4.54 patients per 1.000 inhab-

itants, mean EBS-uptake rate was 2.83 (95% condence interval 2.69

– 2.96). Bivariate OLS spatial regression models revealed migration (R² =

0.499) and multiple deprivation (R² = 0.574) as suitable explanatory fac-

tors for the variance in uptake rates.

Discussion: Substantial dierences in the uptake of genetic counselling

services were observed in the city of Cologne. ese dierences were

shown to be closely related to area-based deprivation and migration levels.

Conclusion: Our results indicate that the social gradient in health care

utilization observed in numerous health care contexts also exists in the

context of familial and hereditary breast and ovarian cancer.

Disclosure Statement: e authors declare no conict of interest.

238

Regional quality conferences of the Hamburg Cancer Registry

(HCR): Evaluation of guideline-based treatment pathways

using the example of radiotherapy after breast-conserving

surgery in patients with invasive breast cancer

Vera Henrichs1; Annemarie Schultz2; Imma Löhden2; Cynthia Erb2;

Alice Nennecke2

1Hochschule für Angewandte Wissenschaft Hamburg, Hamburg, Deutschland

2Freie und Hansestadt Hamburg, Behörde für Wissenschaft, Forschung,

Gleichstellung und Bezirke, Hamburgisches Krebsregister, Hamburg ,

Deutschland

Background: Regional quality conferences of the Hamburg Cancer

Registry (HCR) aim to promote interdisciplinary collegial discussion on

data to further improve quality of oncological care.

According to the current S3 guideline on breast cancer, postoperative

radiotherapy (RT) is the key intervention to reduce the risk of intrama-

mmary recurrence in context of breast-conserving therapy (BCT). As

part of regional quality conferences it was shown that fewer patients than

expected received RT aer BCT in Hamburg. Additional analyses were

performed to verify this statement.

Methods: HCR-registered patients diagnosed with invasive breast can-

cer from 2017 to 2020 with BCT followed by adjuvant RT or not were

included. e observation period encompassed Jan. 1, 2017, through

March 30, 2021.

Result: 76.8% (2,569) of 3,347 patients with invasive breast cancer and

BCT received RT during the observation period in Hamburg. Concerning

23.2% (778) of patients, no evidence of RT was provided.

In Kaplan-Meier analysis, overall survival was signicantly better in

patients with BCT and adjuvant RT compared to patients without RT

(96.2% vs. 89.6% by end of observation; p < .0001, log-rank test). Receiving

adjuvant RT reduced the risk of mortality by 56.6% in patients aer BCT

(HR = .434; 95% CI .265 - .712; p = .001).

Conclusion: Our results indicate that the majority of patients with inva-

sive breast cancer and BCT diagnosed in Hamburg received adjuvant RT

according to guidelines. A quarter of patients lack this evidence, while this

proportion was estimated 10% - 15% by clinicians. As expected, the pos-

itive impact of RT on survival of patients with invasive breast carcinoma

and BCT was conrmed.

In context of the regional quality conferences, decits in care can be

revealed and further research is necessary to investigate reasons for

undertreatment.

Disclosure Statement: e authors declare no conict of interest.

278

Regional dierences in the access to certied cancer care –

The inuence of regional innovation systems in Germany

Tim Brand; Katharina Blankart

CINCH Health Economics Research Center, Universität Duisburg-Essen, Essen,

Deutschland

Background: A central aspect of improving quality of care is the diusion

of innovation from research into practice. One way to facilitate this pro-

cess is program accreditation. By conceptualization, innovation activities

and accreditation require dierent competencies and processes. While

this may hinder the uptake of accreditation, the eect of innovation activ-

ities on the diusion of accreditation is mostly unknown. In this study, we

aim to evaluate this relationship in the context of accredited organ cancer

centers in Germany.

Methods: We perform a retrospective study at district level combining

scientic publications as measures for innovation activities and accred-

itation data for eight cancer sites from 1998-2017. Scientic publication

data was obtained from the National Library of Medicine and mapped to

the authors’ geolocation using the MapAl tool. Regional accreditation

status and timing is provided by the German Cancer Society. We evaluate

the eect of innovation activities on accreditation status, estimating linear

probability models including accreditation type xed eects. We consider

cancer incidence, gross domestic product and hospital competition as

confounders of innovation activities.

Results: Regions with any publications have a 9.6% higher probability to

have at least one accredited cancer center. Sub-group analysis for breast

cancer suggests that about 60% of districts had no breast cancer publi-

cations before initiation of the accreditation program. In comparison to

these district, districts with up to 20 publications (90th percentile) had

on average 0.174 accredited centers more one year and 0.25 centers more

three years aer initiation. Districts in the highest 10% by publication

activity had on average 0.377 accredited centers more one year and 0.846

centers more three years aer initiation.

Discussion: Innovation activities and accreditation are no contradictory

strategies in specialized cancer care. New incentives for accreditation

might increase quality of cancer care in regions with fewer innovation

activities.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 135

449

Low rates of inuenza and pneumococcal vaccination among

cancer patients

Simon Lendowski1; Corinna Sophie Marheinecke2; Daniel R. Quast3;

Eleni Kourti1; Stephanie Pfänder2; Anke Reinacher-Schick1; Oliver Overheu1

1Klinik für Hämatologie und Onkologie mit Palliativmedizin, St. Josef-Hospital

Bochum, Klinikum der Ruhr-Universität Bochum, Bochum, Deutschland

2Abteilung für Molekulare & Medizinische Virologie, Ruhr-Universität Bochum,

Bochum, Deutschland

3Klinik für Innere Medizin, St. Josef-Hospital Bochum, Klinikum der Ruhr-

Universität Bochum, Bochum, Deutschland

Background: Cancer patients, especially those under chemotherapy, are

at an increased risk for respiratory infections, including inuenza and

pneumococcal infections, which are both vaccine preventable. However,

low vaccination rates have been reported.1

Methods: Between April and August 2021 125 cancer patients at our

university cancer center completed a questionnaire containing multiple

choice questions and ten eleven-level Likert items ranging from 1 (“totally

disagree”) to 11 (“totally agree”) in order to assess rates of previous inu-

enza and pneumococcal vaccinations as well as the patient’s attitudes

towards vaccinations in general.

Result: Mean age was 65.5 years (24-86), 46% were female. e majority

(82%) had solid tumors. Almost all (88%) were on active anti-tumor ther-

apy, mainly chemotherapy (75%). 58% received an inuenza vaccination

at least once within the last 5 years, whereas only 30% had a pneumococcal

vaccine. Rate of inuenza vaccination among women was statistically sig-

nicant higher (70% vs. 48%, p=0.0064), while it did not dier in regard of

pneumococcal vaccine (28% among men vs. 35% among women, p=0.21).

Most patients completely disagreed with “being against vaccinations in

general” (80%; mean 1,81; statistically signicant dierence on Likert item

between men vs. women: mean 1.45 vs. 2.26, p=0.0427).

Discussion: We report higher rates of vaccination against both inuenza

and pneumococcal infections than previous studies. Nonetheless, rates

remain low, especially among men.

Conclusion: Further research is necessary regarding factors associated

with hesitancy to receive vaccinations as well as to determine potentials of

improvement of vaccine coverage. Also gender dierence should be taken

into account.

Reference:

1 Monier A, Puyade M, Hernanz MPG, Bouchaert P, Leleu X, Tourani JM, et al.

Observational study of vaccination in cancer patients: How can vaccine covera-

ge be improved? Med Mal Infect. 2020;50(3):263-8.

Disclosure Statement: e authors declare no conict of interest.

473

Perception and expectations of preventive health behavior

in medical institutions during the SARS-CoV-2 pandemic

in Germany: Results of a cross-sectional web-based survey

in women with an increased hereditary risk for breast and

ovarian cancer

Roxana Schwab; Annika Droste; Annette Hasenburg

University Medical Center Mainz, Department of Gynecology and Obstetrics,

Mainz, Deutschland

Background: Patients with cancer are at higher risk to be infected by

SARS-CoV-2, are more likely to develop a severe COVID-19 illness, and

are more likely to die as a result of COVID-19. us, several strategies

were proposed to mitigate the SARS-CoV-2 pandemic crisis with respect

to people at higher risk, such as implementing strict personal precautions

in cancer patients or cancer survivors.

Methods: To assess the expectations and perspectives of women with an

increased hereditary risk for breast and ovarian cancer regarding mea-

sures to prevent infection and implement environmental control during

the SARS-CoV-2 pandemic, a web-based survey was placed on internet

platforms of support groups between 29th January and 22th April 2021.

Missing data were composed of those patients who did not answer the

question or who did not have a clear opinion regarding the topic. Data are

presented as frequencies of selected items.

Result: 37.5% of participants stated, that they would like to be informed

about the hygiene concept of the health care institution and 20.3%

reported that this information would have changed their own behavior.

To prevent the spread of the virus, 57.8% of respondents approved testing

of patients previous to a visit to a health care facility and 95.3% stated,

that health care professionals should be tested on a regular basis. 93.8%

approved the change of appointments to ensure social distancing, but

75.0% would support the possibility to be escorted by a signicant other

during medical appointments. To avoid unnecessary possible exposure,

71.9% of participants endorsed the possibility of virtual patient consulta-

tions. Additionally, 84.4% of respondents expected, that health care per-

sonnel used at least surgical masks, and 68.8% expected, that the health

care personnel used FFP-2 masks.

Discussion: Protecting patients at risk and medical caregivers is a priority

during pandemics.

Conclusion: Our data emphasize the wish and need for reorganization of

health care facilities with the aim to protect patients at risk.

Disclosure Statement: e authors declare the following: RS: Honoraria: Roche

Pharma AG, AstraZeneca, Streamedup!GmbH, AH: Honoraria: AstraZeneca;

Celgen; MedConcept GmbH, Med update GmbH; Medicultus; Pzer; Promedicis

GmbH; Soconsult; Roche Pharma AG; Streamedup!GmbH; Tesaro Bio Germany

GmbH, LEO Pharma Ad Board; PharmaMar; Promedicis GmbH; Roche Pharma

AG; Tesaro Bio Germany GmbH, AstraZeneca, LEO Pharma, MSD Sharp &

Dohme GmbH

523

Real world data (RWD) from the AIO ColoPredict Plus (CPP)

registry (AIO-KRK-0413/ass): Impact of the Sars-CoV-2

pandemic on enrollment of patients (pts.) with colorectal

cancer (CRC) - analysis for the CancerCOVID consortium

Celine Lugnier1; Anna-Lena Kraeft2; Sabine Sommerlatte3; Inke Feder4;

Daniel Benitez2; Eleni Kourti2; Rabia Safaei2; Sarah Wisser4; Olaf Schoer5;

Vitali Heidt6; Wolfgang Knauf7; Christan Teschendorf8; Waldemar Uhl9;

Stefanie Nöpel-Dünnebacke2; Jochen Schmitt10; Jan Schildmann11;

Anke Reinacher-Schick2; Andrea Tannapfel4

1Bochum, St. Josef Hospital Bochum, Ruhr Universität Bochum, Mediznische

Klinik V für Hämatologie und Onkologie mit Palliativmedizin, Bochum,

Deutschland

2Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität

Bochum, Mediznische Klinik V für Hämatologie und Onkologie mit

Palliativmedizin, Bochum, Deutschland

3Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-

Luther Universität Halle-Wittenberg, Uniklinikum Halle, Halle

4Institut für Pathologie - Georgius Agricola Stiftung Ruhr, Institut für

Pathologie - der Ruhr-Universität Bochum am Berufsgenossenschaftlichen

Universitätsklinikum Bergmannsheil , Bochum

5Zentrum für evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und

Medizinische Fakultät Carl Gustav Carus der Technischen Universität Dresden,

Dresden

5Wissenschaftliche Institut der Niedergelassenen Hämatologen und

Onkologen– WINHO GmbH, Köln

7Berufsverband der Niedergelassenen Hämatologen und Onkologen in

Deutschland e.V., Köln

8St. Josef Hospital Dortmund, Mediznische Klinik I, Dortmund

9Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität

Bochum, Allgemin- und Viszeralchirurgie, Bochum

10Zentrum für Evidenzbasierte Gesundheitsversorgung, Universitätsklinikum

und Medizinische Fakultät Carl Gustav Carus an der Technischen Universität

Dresden, Dresden

11Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-

Luther Universität Halle-Wittenberg, Uniklinikum Halle, Halle

Purpose: CRC prognosis has improved through guideline-based care.

COVID-19 pandemic lead to re-allocation of health care resources poten-

tially putting sections of cancer care at a disadvantage. We compared

enrollment and clinical subgroups into our registry before and during the

rst (fw) and second wave (sw) of the COVID-19 pandemic.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts136

Methods: CPP assembles clinical, histo-pathological and molecular

data of pts. with resected CRC. Prospectively enrolled pts. during the

fw (4-6/2020) and the sw (10-12/2020) were analyzed, focusing on total

numbers, age and sex compared to corresponding pre-pandemic intervals

of 2019. Due to site expansion (70 to 161) of CPP we calculated quarterly

counts per site and in relation to total enrollment.

Results: 2221 pts. enrolled into CPP during 2019 and 2020 were included,

47 % female (F) /53 % male (M). Mean age in 2019 was 71.9 years (y) vs

71.6 y in 2020. Mean number of pts. enrolled in CPP with primary diag-

nosis of CRC per site 2019/2020: fw 8,5/6.9 and sw 6.2/5.8. Evaluation for

age showed: 2019%/2020% fw >70 y was 52.5/53.5 and ≤70 y 47.5/ 46.5

respectively; for the sw > 70 y was 45.6/ 53.5; ≤70 y 54.4/46.5. M vs F in fw

2019%/2020% M 50.5/61; F 49.5/39; in sw M 57.6/56; F 42.4/44.

Discussion: CPP did not detect substantial dierences in total counts of

enrolled patients or distribution of age and sex. We detected a slight dip

in enrollment together with a small shi toward men in fw as well as to

elderly pts. in sw. Enrollment of pts. into registries seems to be feasible

even in pandemic situation. Potentially, a possible data bias as preference

of registry enrollment over randomized controlled trials.

Conclusion: Real world data from CPP must be complemented by addi-

tional data for comprehensive assessment of colon cancer care and will

be complemented for nal data presentation in 2022 with data collected

during the third and omicron wave.

is study was supported by the Federal Ministry of Education and

Research

Disclosure Statement: e authors declare no conict of interest.

562

Evaluation of an interventional retrospective study with

oncological training and exercise therapy (OTT) in a health

insurance care contract

Louisa Zimmermann1; Nico De Lazzari1; Freerk Baumann2; Habibe Ercan3;

Sara Man2; Christoph Meyer4; Marion Hammling5; Mitra Tewes1

1Westdeutsches Tumorzentrum, Innere Klinik (Tumorforschung),

Universitätsklinikum Essen

2Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf, Klinik I für

Innere Medizin Onkologie, Universität zu Köln

3Klinik für Psychosomatische Medizin und Psychotherapie , LVR Klinikum Essen,

Universität Duisburg Essen

4Praxiszentrum Elisengalerie, Aachen

5AOK Rheinland/Hamburg

Purpose: To evaluate the cost-eectiveness of the oncological training

and exercise therapy (OTT) in this retrospective interventional study on

cancer patients (pts) on curative and palliative therapy protocols.

Methods: Data provided by a German healthcare provider. Number and

cost of ambulant visits, days and cost of hospitalization, and costs of med-

ication of enrolled pts and a matched control group (CG) were collected

for 9-months aer the begin of the training intervention. Demographics

and diagnoses were documented over the whole 4-year study period. Pts

completing at least 12 of 24 planned training sessions were dened as

intervention group (IG).

Results: From 2015 to 2019 152 pts were recruited for OTT participation.

Of these, 39 completed the intervention, 19 dropped out during training

and 94 enrolled but never participated. Most frequent malignancies were

breast (IG/ CG; 20.5 / 26.9%) and lung cancer (20.5 / 12.8%), and hema-

tological malignancies (20.5 / 15.4%). We observed a tendency towards

better survival in the IG compared to the CG (1-year-survival 94.9 /

78.7%). e IG had a signicantly higher number of ambulant visits and

higher associated costs than the CG (median dierence 371 - 630€ | 8 - 5d;

p<0.0001 - p=0.0069). Furthermore, the IG had signicantly higher costs

of medication (median dierence 265€; p=0.007). e number of inpa-

tient days and costs of hospitalization did not dier signicantly between

groups.

Discussion: e OTT might improve patient mobility, compliance and

therapeutic relationship, as the number of ambulant visits, associated

costs, and cost of medication increased under OTT. is might explain a

tendency towards better survival in the intervention group, although the

need for in-hospital care was not decreased correspondingly.

Conclusions: Tumor patients participating in structured physical training

seek more outpatient medical care without the need for more frequent

hospital admission. e OTT might thus improve compliance and thera-

peutic relationship which might improve morbidity and mortality.

Disclosure Statement: e authors declare the following: Koautoren sind Teilneh-

mer des wissenschalichen Beirates der Krankenkasse.

779

Treating hepatocellular carcinoma (HCC) in Germany – an

health economic perspective

Bernhard Mörtl1,1; Dominik Beier2; Enroci N de Toni3;

Korbinian Hasselmann1; Stefan Munker3; Karin Berger1;

Benedikt Westphalen1

1Klinikum der Universität München (LMU), Medizinische Klinik und Poliklinik III,

München, Deutschland

2InGef – Institute for Applied Health Research Berlin GmbH, Berlin, Deutschland

3Klinikum der Universität München (LMU), Medizinische Klinik und Poliklinik II,

München, Deutschland

Background: Only limited information on epidemiology, resource

consumption, costs from third party payer perspective, and outcomes

observed in routine care (inpatient and outpatient) in Germany exists.

Objective of this study was to evaluate the grade claims data can be used

to ll aforementioned gaps.

Methods: is retrospective cohort study is based on anonymized, lon-

gitudinal German third party payer claims data from 2014 - 2019 (InGef

database). Inclusion criteria: ≥18 years, inpatient / outpatient diagnosis of

HCC (ICD-10-GM C22.0).

Result: In total 818 prevalent patients (pts) with hepatocellular carcinoma

were identied in 2014, 994 pts in 2019. In this cohort the prevalence per

100.000 increased to 29 pts in 2019, compared to 24 pts per 100.000 in

2014. Mean age was 70 years (SD ±10,7), 73% were male. Approximately

86% pts were hospitalized, with mean 3 admissions (SD ±2,7) annually

and mean 32 inpatient days per patient (ppt; ±41,6). Mean annual total

costs were €20.184 ppt in 2014 (median 13.652; range 112 – 213.877) and

€22.935 ppt in 2019 (15.474; 134 – 482.238). Proportion of costs in 2019

exemplary: inpatient care (59%), drug treatment (29%), outpatient care

(8%) and therapeutic aids (4%). In the context of increasing patient num-

bers, the total cost for this cohort increased from €16.5 Mio in 2014 up to

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 137

€22.8 Mio in 2019. e mean annual mortality of the prevalent pts was

30,6%. In a subgroup analysis on incident HCC pts, 67% died within the

rst two years aer diagnosis.

Discussion & Conclusion: e clinical outcome in terms of survival is

poor. Mortality, frequency and length of hospitalization signal a high bur-

den on patients and their families. e level of information provided by

claims data is limited as for example the information on number of treat-

ment lines or tumour status are missing. Despite these limitations, claims

data give a detailed insight into epidemiology, hospitalisation, resource

consumption, costs and mortality of the study cohort.

Disclosure: LMU received a research grant from Roche Pharma AG;

InGef received research funding by LMU.

Disclosure Statement: e authors declare the following: LMU Klinikum (MED

III) received a research grant from Roche; InGef has received research funding by

LMU Klinikum (MED III).

986

On the eects of patient pathways in comprehensive cancer

care - A systematic literature review of evaluation criteria

Peggy Richter1; Lisa Zapfe1

1Technische Universität Dresden, Forschungsgruppe Digital Health, Dresden,

Deutschland

Background: Patient pathways (PPs) are perceived helpful to coordinate

comprehensive cancer care, implement guideline recommendations and

inform patients. e updated S3-guideline for pancreatic cancer now

includes a PP template for pancreatic cancer centers. To advance PP appli-

cation and study their impacts, reliable evaluation criteria are needed.

is study analyses which evaluation criteria for oncological PPs eects

are used so far.

Methods: A systematic literature review was conducted. Pubmed, Scopus,

Web of Science and Academic Search Elite were searched for (patient

pathway OR clinical pathway OR care pathway OR integrated pathway)

AND (evaluat* OR outcome* OR analysis OR assess*), ltering for oncol-

ogy. In total, 29 articles were included. e Leuven Clinical Pathway

Compass was used to categorize evaluation criteria.

Result: Almost all articles evaluated PPs in hospitals. Only one had an

inter-organizational PP scope. Most evaluation criteria are nancial (used

in 90% of the studies, e.g. length of stay, cost savings) and clinical crite-

ria (93%, e.g. complications, mortality, re-admission, clinical outcomes).

Process (45%, e.g. pathway variances, use of procedures) and service cri-

teria (45%, e.g. patient satisfaction, quality of life) were used less oen.

Team criteria occurred the least (17%, e.g. communication, professional

involvement). PPs for gastrointestinal cancers were evaluated most oen.

Discussion: Results show a lack of common evaluation standards for PPs

in cancer care. Criteria addressing key characteristics, i.e. network and

patient focus, are scarce. Further, the comparability of PP evaluation stud-

ies is limited due to undened and varying PP implementation status.

Conclusion: Criteria in use for oncological PP evaluation have limited

perspective and lack comprehensiveness to cover the complexity of PPs

in comprehensive cancer care. An evaluation framework including proce-

dural guidance and criteria also considering dierent PP implementation

levels would allow for PP benchmarking across comprehensive cancer

centers.

Disclosure Statement: e authors declare no conict of interest.

1039

S1 Guideline for prioritisation in gastrointestinal cancer care –

scarcity of ressources in the pandemic context

Anke Reinacher-Schick1; Pompiliu Piso2; Emmannouil Fokas3; Matthias

Ebert4; Tanja Zimmermann5; Ulrich Wedding6; Celine Lugnier1; Anna-Lena

Kraeft1; Olaf Schoer7; Sabine Sommerlatte8; Thomas Birkner9; Sarah

Förster10; Stefan Rolf Benz11; Monika Klinkhammer-Schalke12; Wolfgang

Knauf13; Ralf-Dieter Hofheinz14; Andrea Tannapfel10; Jochen Schmitt9;

Berhard Wörmann15,16; Jan Schildmann17

1Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität

Bochum, Mediznische Klinik V für Hämatologie und Onkologie mit

Palliativmedizin, Bochum

2Barmherzige Brueder Krankenhaus, Regensburg, Abteilung für Chirurgie,

Regensburg

3Goethe Universität Frankfurt , Universitätsklinikum Frankfurt, Klinik für

Strahlentherapie und Onkologie, Frankfurt

4Universitätsmedizin Mannheim, Medizinische Fakultät, Universität Heidelberg,

Medizinischen Klinik II. , Mannheim

5Medizinische Hochschule Hannover , Klinik für Psychosomatik und

Psychotherapie , Hannover

6Universitätsklinikum Jena, Klinik für Innere Medizin II , Abteilung

Palliativmedizin, Jena

7Zentrum für evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und

Medizinische Fakultät Carl Gustav Carus an der Technischen Universität Dresden,

Dresden

8Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-

Luther Universität Halle-Wittenberg, Halle (Saale)

9Zentrum für evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und

Medizinische Fakultät Carl Gustav Carus an der Technischen Universität Dresden,

Dresden

10Institut für Pathologie am Berufsgenossenschaftlichen Universitätsklinikum

Bergmannsheil, Ruhr-Universität Bochum, Bochum

11Krankenhaus Kliniken Böblingen , Klinik für Allgemein-, Viszeral- und

Kinderchirurgie, Böblingen

12Institut für Qualitätssicherung und Versorgungsforschung der Universität

Regensburg , Universität Regensburg , Regensburg

13Berufsverband der Niedergelassenen Hämatologen und Onkologen in

Deutschland e.V. , Köln

14Universitätsklinikum Mannheim, Mannheim Cancer Center, Mannheim

15DGHO Berlin, Deutsche Gesellschaft für Hämatologie und Onkologie e.V.,

Berlin

16Charité Berlin Virchow Campus, Universitätsklinikum Berlin, Medizinische

Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Berlin

17Instituts für Geschichte und Ethik der Medizin, Martin-Luther-Universität Halle-

Wittenberg, Halle (Saale)

Background: e COVID-19 pandemic has led to deviations in all sectors

of cancer care. We present multidisciplinarily approved recommendations

for ethically and empirically based prioritisation of procedures in times of

scarce resources for patients with colorectal and pancreatic cancer.

Methods: e CancerCOVID consortium conducted qualitative and

quantitative studies on ethical challenges and psychosocial stress of

patients and health care professionals in cancer care. For empirical analy-

ses we obtained data from AOK Plus, the main health insurance in Saxony,

AIO (Arbeitsgemeinscha internistische Onkologie) cancer centers, the

institute of Pathology Bochum, the ColoPredict Registry and data of

outpatient care from the BNHO (Berufsverband der Hämatologen und

Onkologen) and Onkotrakt AG. A selective literature review of interna-

tional data and guidelines focussing on the eects of the pandemic on

cancer care and allocation of resources was conducted. Structured group

discussions on justied criteria for prioritisation were held with experts

from oncology, ethics, law and health research. Recommendations for

prioritisation were formulated as S1 guideline with approval of 9 AWMF

Medical Societies, 22 multidisciplinary experts and patient representatives.

Results: e main principle for decisions on prioritisation in times of

scarce resources is the minimisation of individual and aggregated harm.

In case of relevant risk of harm from a possible low priority classication

or postponement prioritization decisions should be made individually for

the respective patients according to the multiple-eyes principle. Decision

making should involve dierent disciplines and professions depending

on local infrastructure. We concretised recommendations for 5 areas in

cancer care.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts138

Conclusion: Guidelines based on a broad multidisciplinary consensus

can give ethically and empirically based support in medical decision mak-

ing when resources are scarce. is can provide relief for decision-makers

and facilitate transparency and trust of patients and population.

Disclosure Statement: e authors declare no conict of interest.

1056

Financial distress of cancer patients in everyday counselling

of social services in Germany. A qualitative focus group study

Sophie Pauge1; Bastian Surmann1; Andrea Züger2; Luise Richter3;

Viktoria Mathies4; Thomas Ernst4; Wolfgang Greiner1; Natalja Menold3;

Eva Winkler2

1Universität Bielefeld, Fakultät für Gesundheitswissenschaften,

Gesundheitsökonomie und Gesundheitsmanagement, Bielefeld, Deutschland

2Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen

(NCT) Heidelberg, Sektion Translationale Medizinische Ethik, Heidelberg,

3Technische Universität Dresden, Institut für Soziologie, Professur für Methoden

der empirischen Sozialforschung, Dresden

4Universitätsklinikum Jena, Klinik für Innere Medizin II, Hämatologie und

Internistische Onkologie, Jena

Background: Financial distress (FD) has an eect on cancer patients’

quality of life and distress [1]. For years, social services have recognized

an increasing need for counselling. A survey of social services identi-

ed a wide range of risk factors and a scattered picture of standardized

approaches to address patients at risk [2]. To better understand current

counselling practice and potential determinants of FD, a qualitative focus

group study with social services was performed.

Methods: A semi-structured focus group with n=4 social service repre-

sentatives from in- and outpatient centers in Germany was conducted. An

interview guideline was developed based on results of systematic reviews

on nancial toxicity [3, 4] and a survey of social services [2] . Transcripts

were analyzed using qualitative content analysis following Kuckartz.

Result: FD is discussed within rst consultations of social services by

default. Representatives recognized several risk factors, which can be clas-

sied into 7 categories: “Finance & work”, “social environment”, “housing”,

“medical & treatment-related factors”, “direct costs” and “individual per-

ception”. e extent and type of approach to address FD varies and is usu-

ally based on personal experiences related to the risk factors. Standardized

screening tools are partly applied and most of them are neither validated

nor do they adequately address FD.

Discussion: Social services express the need for a standardized and prac-

tical screening tool. A validated German tool could support social services

in identifying patients at risk of experiencing FD. It might further support

the development of personalized and coordinated intervention schemes

to alleviate FD.

Conclusion: Financial distress plays an important role counselling and

the demand for coordinated guidance through social services will further

increase.

Literature:

1 Mehlis, K. et al., BMC Cancer, 2020

2 Surmann, B. et al., ZEFQ, 2021

3 Pauge, S.; Surmann, B et al., Cancers, 2021

4 Witte, J. et al. Ann. Oncol., 2019

Disclosure Statement: e authors declare the following: is research is funded

by Deutsche Krebshilfe.

Imaging

Poster

119

Augmented Reality (AR) Computed tomography (CT)-Guided

Liver Punctures: A Phantom Study Introducing A New Type Of

AR System

Vincent Van den Bosch1; Hizirwan Shukri Salim2; Njin-Zu Chen2;

Otto Stroosma2; Philipp Bruners1; Christiane Kuhl1; Peter Isfort1;

Federico Pedersoli1

1Universitätsklinikum Aachen, Klinik für Diagnostische und Interventionelle

Radiologie, Aachen, Deutschland

2Philips, Eindhoven, Niederlande

Background: To investigate the feasibility of a novel AR system using the

HoloLens 2 for performing CT-guided liver interventions.

Methods: A new kind of AR system was developed, oering projection

of CT-images and live optical tracking of the needle position as well as a

bull’s eye view as well as a visualization of the distance to the target. e

experiment was performed using a custom-made abdominal agar-agar

phantom, created from a segmented liver CT (3D Slicer) that contained

digitized target locations. ree radiologists with dierent levels of exper-

tise (resident, junior and senior sta member) performed the experiment,

consisting of 40 punctures. ereof 20 punctures were performed free-

hand and 20 punctures with AR-guidance. A CT-simulator soware was

used for the free hand punctures, sparing long CT-scanning times and so

allowing more punctures to be executed. Semi-structured interviews were

performed aer the experiment. For the statistical analysis, a two-tailed

Wilcoxon Signed-Rank test was performed.

Result: Duration of intervention was signicantly (p<0.05) improved in

all operators with a mean of 110,9 seconds in the free hand punctures and

38,7 seconds in the AR punctures (-65%). e mean accuracy was 4,7 mm

in the free hand group, while being 5,0 mm in the AR group (p>0.05). In

detail, the junior sta member had an improvement of accuracy of 1 mm

using AR (p<0.05), while the others showed no signicant improvement

regarding accuracy. All radiologists rated the AR-setup positively. In par-

ticular, the use of underlying CT imaging, a familiar method in everyday

clinical practice, was rated as advantageous.

Discussion: Like in existing literature, typical limitations of a preclini-

cal phantom study are present. Compared to other studies, a signicant

number of punctures in one experimental setting was performed, taking

advantage of the virtual CT setting.

Conclusion: is AR-system signicantly reduces intervention time and

has furthermore the potential to dramatically reduce the radiation burden

to the patient. ereby accuracy remains comparable.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 139

567

Longitudinal study on MRI and neuropathological ndings:

Neither DSC-perfusion derived rCBVmax nor vessel densities

correlate between newly diagnosed and progressive

glioblastoma

Eike Steidl1; Katharina Filipski2; Elke Hattingen1; Joachim P. Steinbach3;

Gabriele Maurer3

1Institut für Neuroradiologie, Universitätsklinikum Frankfurt

2Neurologisches Institut - Edinger Institut, Universitätsklinikum Frankfurt

3Dr. Senckenbergisches Institut für Neuroonkologie, Universitätsklinikum

Frankfurt

Purpose: When evaluating MRIs for glioblastoma progression, previous

scans are usually included into the review. Nowadays dynamic susceptibil-

ity contrast (DSC)-perfusion is an essential component in MR-diagnostics

of gliomas, since the extent of hyperperfusion upon rst diagnosis cor-

relates with gene expression and survival. We aimed to investigate if this

initial perfusion signature also characterizes the glioblastoma at time of

progression. If so, DSC-perfusion data from the initial diagnosis could be

of diagnostic benet in follow-up assessments.

Methods: We retrospectively identied 65 patients with isocitrate dehy-

drogenase wildtype glioblastoma who had received technically identical

DSC-perfusion measurements at initial diagnosis and at time of rst pro-

gression. We determined maximum relative cerebral blood volume values

(rCBVmax) by standardized re-evaluation of the data including leakage

correction. In addition, the corresponding tissue samples from 24 patients

were examined histologically for the maximum vessel density within the

tumor. Dierences (paired t-test/ Wilcoxon matched pairs test) and cor-

relations (Spearman) between the measurements at both timepoints were

calculated.

Results: e rCBVmax was consistently lower at time of progression com-

pared to rCBVmax at time of rst diagnosis (p<.001). ere was no cor-

relation between the rCBVmax values at both timepoints (r=.12). ese

ndings were reected in the histological examination, with a lower vessel

density in progressive glioblastoma (p=.01) and no correlation between

the two timepoints (r=-.07).

Conclusion: Our results suggest that the extent of hyperperfusion in glio-

blastoma at rst diagnosis is not a sustaining tumor characteristic. Hence,

the rCBVmax at initial diagnosis should be disregarded when reviewing

MRIs for glioblastoma progression.

Disclosure Statement: e authors declare no conict of interest.

873

Ultrasound guided biopsy of the mediastinum

Thorsten Nitsch; Julia Lanznaster; Preißler Sieglinde;

Elisabeth Neuwirth; Thomas Südho

Klinikum Passau, II. Med Klinik, Passau, Deutschland

Background: Mediastinal masses are oen an expression of an aggressive

disease. For this reason, rapid histology acquisition is important, since reli-

able histology forms the basis for further therapy planning. Sonography

is a widely available and gentle method that expands the possibilities of

rapid histology acquisition, but there is little data of sono.-guided biopsy

of the mediastinum. We report here on the eectiveness and complication

rate of this method.

Methods: is is a retrospective analysis of sono.-guided mediastinal

biopsies in our clinic. Ultrasound machine: Toshiba Aplio 400, later i800.

Depending on the location, the puncture was performed with a “convex

array” puncture probe or with a linear probe using the “freehand” tech-

nique. We used true-cut needles (16G to 18G) and a 10F drain. e biop-

sies were performed under local anesthesia and aseptic conditions. On

average, three biopsies and one cytology were performed. Complications

were classied into three grades: 1 for minor to 3 for severe complications.

Result: We performed 31 punctures of the mediastinum. e masses

ranged in size from 1.5 to 7.8 cm. In 27 cases (87%) a reliable histology

could be obtained, so that no further intervention was necessary. In two

cases, the histology could be obtained by sono-repuncture or CT-guided

puncture. In two cases the histology had to be claried by surgery. A com-

plication was recorded in only one case with slight pain. Histology results:

hm B-NHL:6, Adeno-NSCLC:5, SCLC:3, Hodgkin:3, hm T-NHL:2,

T-ALL:2, Squamous CUP:1, Anaplast SD-Ca:1, Mammaca :1, nm NHL:1,

abscess:1, thymoma:1, unspec:2

Conclusion: Base on our results we concluded that ultrasound-guided

biopsy of the mediastinum is a reliable and gentle method with a reliable

histology in 87% of the cases and slight complications (pain) in one case

(3%). Furthermore it is widely available and can therefore be used quickly

and in a time-saving manner. It can be performed on the bedside and in

an upright position in the oen highly symptomatic/dyspnoeic patients, it

is cost-eective and saves radiation.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts140

Leukemia, Myelodysplasia, and Transplantation

Best-of-Abstract-Vortrag

287

Survival outcomes from the QUAZAR AML-001 trial with

oral azacitidine (Oral-AZA) for patients with acute myeloid

leukemia (AML) in remission by disease subtype, cytogenetic

risk, and NPM1 mutation status at diagnosis (Dx)

Michael Pfeilstöcker1; Hartmut Döhner2; Andrew Wei3,4; Gail Roboz5,6;

Pau Montesinos7; Felicitas Thol8; Ignazia La Torre9; Barry Skikne10,11;

Wendy See-Zepeda10; Manuel Ugidos12; Alberto Risueño12; CL Beach10;

Daniel Menezes10

1Hanusch Hospital, Vienna, Österreich

2Universitätsklinikum Ulm, Ulm, Deutschland

3The Alfred Hospital, Melbourne, Australien

4Monash University, Melbourne, Australien

5Weill Cornell Medicine, New York, USA

6New York Presbyterian Hospital, New York, USA

7Hospital Universitari i Politècnic La Fe, Valencia, Spanien

8Medizinische Hochschule Hannover, Hannover, Deutschland

9Celgene, a Bristol-Myers Squibb Company, Boudry, Schweiz

10Bristol Myers Squibb, Princeton, USA

11University of Kansas Medical Center, Kansas City, USA

12BMS Center for Innovation and Translational Research Europe (CITRE), a Bristol-

Myers Squibb Company, Seville, Spanien

Background: In the phase 3 QUAZAR AML-001 trial, Oral-AZA main-

tenance therapy signicantly improved overall and relapse-free survival

(OS/RFS) vs placebo (PBO) in older patients (pts) in remission (median

[med] 24.7 vs 14.8 mo; P<0.001). We assessed OS/RFS in QUAZAR AML-

001 pt subgroups dened by AML subtype (de novo/secondary), cytoge-

netic risk (intermediate [int] or poor), and NPM1/FLT3 mutational status

at Dx.

Methods: Within 4 mo of achieving rst CR/CRi, pts were randomized to

Oral-AZA 300 mg or PBO x14d/28d cycles. Measurable residual disease

(MRD) was assessed at screening (cuto ≥0.1%).

Result: In 429/472 pts (91%) with de novo AML, Oral-AZA signicantly

increased OS vs PBO (med 23.2 vs 14.6 mo; hazard ratio [HR] 0.73;

P=0.007) and RFS (10.2 vs 4.9 mo; HR 0.66; P<0.001). ere was a trend

for better OS in pts with secondary AML (n=43) with Oral-AZA (28.2 vs

15.7 mo; HR 0.58; P=0.11) and signicantly longer RFS (4.7 vs 2.4 mo;

HR 0.47; P=0.012). For pts with int-risk cytogenetics (86%), OS was sig-

nicantly better with Oral-AZA (25.4 vs 15.9 mo; HR 0.73; P=0.009), as

was RFS (11.0 vs 5.8 mo; HR 0.66; P<0.001). In poor-risk pts (14%) there

were trends for better OS with Oral-AZA vs PBO (13.9 vs 7.4 mo; HR

0.61; P=0.06), and RFS (4.6 vs 3.7 mo; HR 0.63; P=0.08). At Dx, 29.2%

(137/469) had NPM1mut, 9.8% (48) had FLT3-ITD, and 6% (30) had

NPM1mut and FLT3-ITD. In the PBO arm, NPM1mut vs NPM1wt was prog-

nostically favorable for RFS (6.9 vs 4.6 mo; HR 0.64; P=0.008) with a trend

for better OS (15.9 vs 14.6 mo; HR 0.75; P=0.10). Med OS for NPM1mut

pts was much longer with Oral-AZA vs PBO (46.1 vs 15.9 mo; HR 0.57;

P=0.014), as was RFS (23.2 vs 6.9 mo; HR 0.55; P=0.001). More pts with

NPM1mut were MRD– (61.7%) vs MRD+ (38.4%) at screening (P=0.018).

In NPM1wt pts, Oral-AZA signicantly increased OS (19.6 vs 14.6 mo; HR

0.77; P=0.036) and RFS (7.7 vs 4.6 mo; HR 0.69; P=0.003).

Discussion: Oral-AZA signicantly improved OS/RFS for pts with de

novo AML and int-risk cytogenetics. Pts with NPM1mut had an OS benet

of >2.5 yrs vs PBO.

Conclusion: NPM1mut is prognostically favorable and predictive of

increased OS with Oral-AZA.

Disclosure Statement: e authors declare the following: MP reports honoraria

for speaker services and consultancy for Abbvie, Astellas, BMS, Jazz, Novartis, and

Takeda; research funding: BMS.

Poster

Bone marrow derived stromal cells from Myelodysplastic

Syndromes are altered but not clonally mutated in vivo

Johann-Christoph Jann1; Eva Altrock1; Nanni Schmitt1; Vladimir Ryabov1;

Qingyu Xu1; Ali Darwich1; Georgia Metzergoth1; Wolf-Karsten Hofmann1;

Daniel Nowak1

1Universitätsmedizin Mannheim, III. Medizinische Klinik, Mannheim

Purpose: Increasing evidence suggests that the pathogenesis of

Myelodysplastic Syndromes (MDS) is not only driven by the hematopoi-

etic compartment but also the bone marrow (BM) microenvironment.

Seminal studies in murine models have demonstrated that isolated muta-

tions in the BM niche can disrupt the non-mutated hematopoietic com-

partment and induce MDS-like diseases. An unanswered question has

therefore been whether primary MDS in humans is possibly also associ-

ated with acquired mutations in the BM stroma.

Methods: In order to address this hypothesis, we performed a compre-

hensive whole exome sequencing study on BM derived in vitro expanded

mesenchymal stromal cells (MSCs) of n=98 MDS and myeloid neopla-

sia patients and a control group of n=20 healthy individuals. In addition,

MSCs in serial culture passages and dierent BM aspirations from the

same patients were sequenced in order to investigate whether acquired

mutations in MSCs were artefacts of the ex vivo expansion. Putatively high

condence mutations were further backtracked by deep re-sequencing in

primary sorted CD45-CD235a-CD31-CD271+ BM cells in n=9 cases.

Results: We discovered multiple recurrently acquired mutations in

expanded MSCs of MDS patients in genes such as ZFX (n=8/98), RANK

(n=5/98), and others. Expanded MSCs from MDS patients displayed a

higher mutational burden and distinct mutational signatures. However, all

validation experiments in serial cultures and primary sorted MSCs indi-

cated that the discovered mutations were expanded by in vitro culture but

not present in relevant cell populations in the primary BM.

Conclusion: us, we conclude that there is no evidence for clonal muta-

tions in the BM stroma of MDS patients.

Disclosure Statement: e authors declare no conict of interest.

268

Late toxicities after total-body irradiation – a long-term

analysis of hematological patients

Michael Oertel1; Jonas Martel1; Jan-Henrik Mikesch2; Matthias Stelljes2;

Hans Theodor Eich1

1Klinik für Strahlentherapie - Radioonkologie, Universitätsklinikum Münster,

Münster, Deutschland

2Knochenmarktransplantationszentrum, Universitätsklinikum Münster, Münster,

Deutschland

Background: Total-body irradiation (TBI) enables an eective myeloab-

lative conditioning before allogeneic stem cell transplantation. With the

whole body being the radiation target, various toxicities may arise, which

prompted us to investigate long-term sequelae of this treatment concept

in a large patient cohort [1]

but is accompanied by relevant (long-term.

Methods: An institutional retrospective search identied 322 patients

with acute leukemia or myelodysplastic syndrome with a minimum fol-

low-up of one year (median 68 months). Median age at transplantation

was 47 years and TBI was done with 8 Gy (236 patients) or 12 Gy (82

patients) in most cases.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 141

Results: Pulmonary, cardiac, ocular, neurological and renal toxicities

were reported in 23.9 %, 14.3 %, 23.6 %, 23.9 % and 20.2 % of all patients,

respectively. Most of these side eects were grade 1-2 (64.9 % - 89.2 %) for

the respective categories. e use of 12 Gy TBI was associated with a sig-

nicant increase in ocular toxicities (p=0.013) and in severe mucositis (p

< 0.001). In addition, chronic gra versus host disease was accompanied

by a shortened pulmonary-toxicity free interval (133.0 months (chronic)

vs. 144.9 months (acute) vs. 183.2 months (none); p<0.001) and by an

increase in ocular toxicity (relative risk 5.88; p<0.001).

Discussion: Although diverse toxicities were observed, the majority was

mild to moderate. An increased TBI dose, in balance with an adapted che-

motherapy regimen, does not lead to a disproportional rise in side eects,

with ocular toxicities and mucositis being the only toxicities increased in

the 12 Gy group.

Conclusion: Total-body irradiation bears a diverse but manageable toxic-

ity prole. Long term follow-up is mandatory for a complete evaluation of

the resulting side eects.

Indication of source:

1. Oertel M et al (2021) Cancers 13:2946. https://doi.org/10.3390/can-

cers13122946

Disclosure Statement: e authors declare no conict of interest.

A preliminary analysis has been presented at the 27th Annual Meeting of the

German Society of Radiation Oncology. Data on pulmonary toxicities were

published before [1].

281

Luspatercept Reduces Red Blood Cell Transfusions (RBCT) in

Patients with Lower-Risk Myelodysplastic Syndromes (LR-

MDS) Regardless of Baseline Transfusion Burden (TB) in the

MEDALIST Study

Uwe Platzbecker1; Guillermo Garcia-Manero2; Pierre Fenaux3;

Rena Buckstein4; Valeria Santini5; Maria Diez-Campelo6; Derek Tang7;

Rodrigo Ito8; Shannon Fabre7; Emily Mantovani8; Roberto Zooli9;

Dimana Miteva7; Christina Hughes7; Wasiulla Khan8; Rami S. Komrokji10;

Ulrich Germing11

1University Hospital Leipzig, Medical Clinic and Policlinic 1, Hematology and

Cellular Therapy, Leipzig, Deutschland

2The University of Texas MD Anderson Cancer Center, Department of Leukemia,

Houston, USA

3Université Paris 7, Service d’Hématologie Séniors, Hôpital Saint-Louis, Paris,

Frankreich

4Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Kanada

5University of Florence, MDS Unit, Azienda Ospedaliero Universitaria Careggi,

Florence, Italien

6University Hospital of Salamanca, Hematology Department, Institute of

Biomedical Research of Salamanca, Salamanca, Spanien

7Bristol Myers Squibb, Princeton, USA

8Formerly Bristol Myers Squibb, Princeton, USA

9Bristol Myers Squibb, Braine-l’Alleud, Belgien

10Mott Cancer Center, Tampa, USA

11University Hospital of Düsseldorf, Düsseldorf, Deutschland

Background: MEDALIST (NCT02631070) is a randomized, phase 3

trial to assess the ecacy and safety of luspatercept in patients (pts) with

anemia due to LR-MDS with ring sideroblasts. Luspatercept reduced red

blood cell TB, with signicant rates of transfusion independence (Fenaux

et al. NEJM 2020;382:140–51). Using data from MEDALIST we assess the

eect of luspatercept on cumulative RBCT units and visits in LR-MDS pts

according to their baseline TB levels.

Methods: Eligible pts were refractory, intolerant, or unlikely to respond

to erythropoiesis-stimulating agents, and required regular RBCT (≥ 2

units/8 weeks [wks]) in the 16 wks prior to randomization. Overall, 229

pts were randomized 2:1 to receive either luspatercept (n = 153) or pla-

cebo (n = 76) every 3 wks through to clinical assessment visit at Wk 25

(data cuto: July 1, 2019). Mean cumulative RBCT units and visits were

estimated. Luspatercept responders were dened as pts achieving RBC-TI

≥ 8 wks during Wks 1–24; low TB (LTB) pts received < 6 RBCT units/8

wks and high TB (HTB) pts received ≥ 6 RBCT units/8 wks at baseline.

Result: LTB and HTB pt numbers were comparable in the luspatercept

and placebo arm at baseline; 87/153 (56.9%) in luspatercept vs 43/76

(56.6%) in placebo were LTB, whereas 66/153 (43.1%) vs 33/76 (43.4%)

were HTB. Mean cumulative RBCT units received (95% condence inter-

val [CI]) in LTB pts were 6.8 (5.6–8.4) in the luspatercept arm (n = 81/87)

vs 13.2 (11.5–15.2) in placebo (n = 38/43); and for HTB pts, were 17.2

(15.1–19.6) in the luspatercept group (n = 47/66) vs 24.2 (21.3–27.4) in

placebo (n = 30/33). Mean cumulative RBCT visits (95% CI) in LTB pts

were 4.0 (3.3–4.8) in the luspatercept arm (n = 81/87) vs 7.2 (6.3–8.3) in

placebo (n = 38/43); and for HTB pts were 9.4 (8.3–10.7) in the luspater-

cept arm (n = 47/66) vs 12.5 (11.0–14.2) in placebo (n = 30/33).

Conclusion: In MEDALIST, luspatercept reduced RBCT units and visits

relative to placebo over the rst 24-wk period in pts with LR-MDS regard-

less of their baseline TB. is abstract was presented at EHA 2021 (Garcia-

Manero et al. HemaSphere 2021;5[S2]:EP920).

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

282

Benet of Continuing Luspatercept Therapy in Patients with

Lower-Risk Myelodysplastic Syndromes (LR-MDS) Who Did

Not Achieve Red Blood Cell Transfusion Independence (RBC-

TI) by Week 25 in the MEDALIST Study

Uwe Platzbecker1; Ulrich Germing2; Pierre Fenaux3; Rena Buckstein4;

Valeria Santini5; Maria Diez-Campelo6; Derek Tang7; Rodrigo Ito8;

Shannon Fabre7; Emily Mantovani8; George Zhang7; Xianwei Ha7;

Dimana Miteva7; Christina Hughes7; Wasiulla Khan8; Rami S. Komrokji9;

Guillermo Garcia-Manero10

1University Hospital Leipzig, Medical Clinic and Policlinic 1, Hematology and

Cellular Therapy, Leipzig, Deutschland

2University Hospital of Düsseldorf, Düsseldorf, Deutschland

3Université Paris 7, Service d’Hématologie Séniors, Hôpital Saint-Louis, Paris,

Frankreich

4Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Kanada

5University of Florence, MDS Unit, Azienda Ospedaliero Universitaria Careggi,

Florence, Italien

6University Hospital of Salamanca, Hematology Department, Institute of

Biomedical Research of Salamanca, Salamanca, Spanien

7Bristol Myers Squibb, Princeton, USA

8Formerly Bristol Myers Squibb, Princeton, USA

9Mott Cancer Center, Tampa, USA

10The University of Texas MD Anderson Cancer Center, Department of Leukemia,

Houston, USA

Background: MEDALIST (NCT02631070) is a randomized, place-

bo-controlled phase 3 trial to assess the ecacy and safety of luspatercept

in patients (pts) with anemia due to LR-MDS with ring sideroblasts. e

primary endpoint was RBC-TI ≥ 8 weeks (wks) during Wks 1–24 (Fenaux

et al. NEJM 2020;382:140–51). Here we assess the clinical benet of con-

tinued luspatercept treatment for pts who did not achieve the primary

endpoint in the MEDALIST trial.

Methods: Eligible pts were refractory, intolerant, or unlikely to respond

to erythropoiesis-stimulating agents and required regular RBC transfu-

sions (≥ 2 units/8 wks) in the 16 wks pre-randomization. Pts were ran-

domized 2:1 to receive luspatercept (n = 153) or placebo (n = 76) every

3 wks to clinical assessment at Wk 25. is analysis includes pts who did

not achieve the primary endpoint on luspatercept but continued treat-

ment (data cuto: July 1, 2019). Every 24 wks, transfusion burden (TB),

serum ferritin (SF) levels, and hematologic improvement-erythroid (HI-

E) response (dened as ≥ 4 units/8 wks decrease in RBC transfusions [≥ 4

RBC units/8 wks baseline TB] or ≥ 1.5 g/dL increase in hemoglobin/8 wk

[< 4 RBC units/8 wks baseline TB]) were assessed.

Result: Of 68 pts who did not achieve the primary endpoint, 11 (16.2%)

achieved RBC-TI ≥ 8 wks in Wks 25–48; 36 experienced a mean decrease

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts142

of 1.3 RBC units transfused vs baseline. 30/68 (44.1%) pts achieved SF

reduction vs baseline in Wks 25–48, and 7/39 (17.9%) shied from ≥ 1,000

µg/L SF level at baseline to < 1,000 µg/L. In Wks 1–48, 41/68 (60.3%) pts

achieved ≥ 50% RBC TB reduction vs baseline for ≥ 8 wks; 32/68 (47.1%)

pts achieved HI-E. By data cuto, 41/68 (60.3%) pts achieved ≥ 50%

reduction in TB vs baseline for ≥ 8 wks, 15/68 (22.1%) achieved RBC-TI ≥

8 wks, and 33/68 (48.5%) achieved HI-E.

Conclusion: A range of clinical improvements, including reduced TB

and SF, and TI, were achieved by a considerable proportion of pts in the

MEDALIST study who did not achieve the primary endpoint, but con-

tinued to receive luspatercept. is abstract was presented at EHA 2021

(Germing et al. HemaSphere 2021;5[S2]:EP915).

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

323

Histone demethylase KDM4C prevents cellular senescence in

JAK2-mutated neoplasms

Philipp Ernst1,2; Laura Kirchner3; Tina. M. Schnöder3; Nicolas Huber3;

Florian Perner4; Theresa Eifert3; Chen-Jen Hsu3; Nuria Tubío-Santamaría3;

Martin Ungelenk5; Christian A. Hübner5; Astrid Tannert6;

Joachim H. Clement1; Andreas Hochhaus1; Florian H. Heidel3,7

1Universitätsklinikum Jena, Innere Medizin 2, Hämatologie und Onkologie, Jena,

Deutschland

2Universitätsklinikum Jena, Forschungsprogramm „Else Kröner-

Forschungskolleg AntiAge“, Jena, Deutschland

3Universitätsmedizin Greifswald, Innere Medizin 2, Hämatologie, Onkologie,

Stammzelltransplantation und Palliativmedizin, Greifswald, Deutschland

4Dana-Farber Cancer Institute, Department of Pediatric Oncology, Harvard

University, Boston, USA

5Universitätsklinikum Jena, Institut für Humangenetik, Jena, Deutschland

6Leibniz-Institut für Photonische Technologien, Labor für Biophotonik und

Bildgebung, Jena, Deutschland

7Fritz-Lipmann-Institut, Leibniz-Institut für Altersforschung, Jena, Deutschland

Background: JAK2 V617F mutations are associated with myeloprolifer-

ative neoplasms (MPN). Current therapeutic options are ineective to

eradicate JAK2-mutated clones. Hence, MPN patients are at risk of pro-

gressing to secondary acute myeloid leukemia. We sought to determine

genetic vulnerabilities that may prevent persistence and progression of

JAK2-mutated clones.

Methods: Genome-scale lentiviral CRISPR-Cas9 screen. Proliferation

and cell growth competition assay. Transcriptome analysis using RNA-

sequencing. Senescence screen using SA-ßGal assay, laser scanning

microscopy and Western blot. In vivo KDM4C CRISPR-Cas9 knockout

using NXG Mouse Xenogra.

Result: Using genome-scale CRISPR-Cas9 screen KDM4C showed depen-

dence in HEL cells irrespective of co-treatment with Ruxolitinib. Genetic

deletion of KDM4C in human and murine JAK2-mutated cells led to sig-

nicant loss of proliferative advantage compared to non-deleted controls.

Transcriptome analyses on HEL cells following KDM4C-deletion showed

signicant deregulation of senescence associated genes. GSEA revealed

also enriched PI3K/AKT/mTOR and NF-κB signaling. A signicant

increase in SA-ßGal and p21 expression was detected. NXG mice with

JAK2-mutated leukemia and KDM4C-KO showed signicantly improved

survival compared to non-targeting controls.

Discussion: Upon treatment with Ruxolitinib, JAK2-mutated cells sur-

vived depending on KDM4C expression. In vivo models of AML have

shown delayed disease development following deletion of KDM4C. e

evasion of senescence by KDM4C in JAK2-mutated cells observed here

has been described so far in melanocytic cells, and its loss was also associ-

ated with loss of H3K9me3.

Conclusion: JAK2-mutated cells are dependent on KDM4C activity irre-

spective to JAK-inhibitor treatment. Inhibition of KDM4C results in a

proliferative disadvantage of JAK2-mutant cells, which can be explained

by induction of cellular senescence. Sequential therapy combining

KDM4C inactivation and senolysis may represent a promising therapeutic

approach for JAK2-mutated MPN.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

374

First Interim Analysis Of ALPINE Study: Results Of A Phase 3

Randomized Study Of Zanubrutinib Vs Ibrutinib In Patients

With Relapsed / Refractory Chronic Lymphocytic Leukemia /

Small Lymphocytic Lymphoma (CLL / SLL)

Peter Hillmen1; Barbara Eichhorst2; Jennifer R. Brown3; Nicole Lamanna4;

Susan O’brien5; Constantine S. Tam6,7,8,9; Lugui Qiu10; Maciej Kazmierczak11;

Keshu Zhou12; Martin Šimkovič13,14; Jiri Mayer15; Amanda Gillespie-

Twardy16; Mazyar Shadman17,18; Alessandra Ferrajoli19; Peter S. Ganly20;

Robert Weinkove21,22; Tommi Salmi23; Meng Ji24; Jessica Yecies23;

Kenneth Wu24; William Novotny23; Jane Huang23; Wojciech Jurczak25

1St James’s University Hospital, Leeds, Vereinigtes Königreich

2Universität zu Köln, Center for Integrated Oncology, Köln, Deutschland

3Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, USA

4The Herbert Irving Comprehensive Cancer Center, Columbia University, New

York, USA

5The Chao Family Comprehensive Cancer Center, University of California,

Orange, USA

6Peter MacCallum Cancer Centre, Melbourne, Australien

7Universität Melbourne, Parkville, Australien

8St. Vincent’s Hospital Melbourne, Fitzroy, Australien

9Royal Melbourne Hospital, Parkville, Australien

10Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin,

China, VR

11Karol-Marcinkowski-Medizinische-Universität Posen, Department of

Hematology and Bone Marrow Transplantation, Poznań, Polen

12Aliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital,

Zhengzhou, China, VR

13Fakultní nemocnice Hradec Králové, 4th Department of Internal Medicine -

Hematology, Hradec Králové, Tschechische Republik

14Karls-Universität, Faculty of Medicine, Prague, Tschechische Republik

15Masaryk-Universität, University Hospital, Department of Internal Medicine-

Hematology and Oncology, Brno, Tschechische Republik

16Blue Ridge Cancer Care - Roanoke, Roanoke, USA

17Fred Hutchinson Cancer Research Center, Seattle, USA

18Universität von Washington, Department of Medicine, Seattle, USA

19University of Texas MD Anderson Cancer Center, Department of Leukemia,

Houston, USA

20Christchurch Hospital , Department of Haematology, Christchurch, Neuseeland

21Wellington Blood and Cancer Centre, Capital & Coast District Health Board,

Wellington, Neuseeland

22Cancer Immunotherapy Programme, Malaghan Institute of Medical Research,

Wellington, Neuseeland

23BeiGene USA, Inc., San Mateo, USA

24BeiGene (Beijing) Co., Ltd., Beijing, China, VR

25Maria Skłodowska-Curie Institute of Oncology, Krakow, Polen

e increased specicity of zanubrutinib (zanu) was hypothesized to min-

imize toxicities related to ibrutinib (ibr) o-target inhibition, and more

complete and sustained BTK occupancy by zanu may improve ecacy

outcomes. Activity and tolerability of zanu in patients (pts) with CLL/SLL

has been demonstrated in early phase CLL/SLL trials. ALPINE (BGB-

3111-305; NCT03734016) is a global, randomized, phase 3 study compar-

ing zanu vs ibr in pts with relapsed/refractory (R/R) CLL/SLL. We present

results of a preplanned interim analysis of the ALPINE study scheduled

~12 months aer the rst 415 pts were enrolled.

Patients were randomly assigned 1:1 to receive zanu 160 mg BID or ibr

420 mg QD until disease progression. Randomization was stratied by age

(<65 years vs ≥65 years), geographic region, refractory status, and del17p/

TP53 mutation status. e primary endpoint was ORR per investigator,

using 2008 iwCLL guidelines and Lugano criteria for SLL.

Between 1 Nov 2018 and 20 Dec 2019, 415 pts were randomized. At a

median follow-up of 15 months, ORR was signicantly higher with zanu

vs ibr (78.3% vs 62.5%, 2-sided P=0.0006). ORR was higher in pts with

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 143

del11q (83.6% vs 69.1%) and del17p (83.3% vs 53.8%) with zanu, as were

overall 12-month PFS (94.9% vs 84.0%) and OS rates (97.0% vs 92.7%).

e rate of atrial brillation/utter was signicantly lower with zanu (2.5%

vs 10.1%, 2-sided P=0.0014). Rates of major bleeding (2.9% vs 3.9%) and

adverse events leading to discontinuation (7.8% vs 13.0%) or death (3.9%

vs 5.8%) were also lower with zanu. Neutropenia was more common with

zanu (28.4% vs 21.7%); while grade ≥3 infections were lower with zanu

(12.7% vs 17.9%).

In this interim analysis, zanu had a superior response rate, improved

OS and PFS, and a lower rate of atrial brillation/utter vs ibr in pts with

R/R CLL/SLL.

e ALPINE study met its primary endpoint and conrmed that with

more complete and sustained BTK occupancy and more selective BTK

inhibition than ibr, zanu results in improved ecacy and safety outcomes

in pts with R/R CLL/SLL.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

956

Preliminary Safety and Ecacy Of BGB-11417, a Potent and

Selective B-Cell Lymphoma 2 (BCL2) Inhibitor, in Patients (Pts)

with Acute Myeloid Leukemia (AML)

Jake Shortt1; Uwe Platzbecker2; Shuh Ying Tan3; Paul Cannell4;

Teng Fong Ng5; Chun Yew Fong6; Sundra Ramanathan7; Rajeev

Rajagopal8; Sophie Leitch9; Robin Gasiorowski10; Carolyn Grove11;

Douglas Lenton12; Peter Tan13; Courtney Dinardo14; Ming Tat Ling15; Si

Cheng15; Yuan Liu15; Melannie Co15; Wai Y. Chan15; David Simpson15;

Andrew H. Wei13,16

1Monash University and Monash Health, School of Clinical Sciences, Clayton,

Australien

2Leipzig University Hospital, Leipzig, Deutschland

3St Vincent’s Hospital Melbourne, Fitzroy, Australien

4Fiona Stanley Hospital, Murdoch, Australien

5Gold Coast University Hospital, Southport, Australien

6Austin Health, Heidelberg, Australien

7The Saint George Hospital-Kogarah, Kogarah, Australien

8Middlemore Hospital, Auckland, Neuseeland

9North Shore Hospital, Auckland, Neuseeland

10Concord Repatriation General Hospital, Concord West, Australien

11Linear Clinical Research & Sir Charles Gairdner Hospital, Nedlands, Australien

12Orange Health Service (Central West Cancer Care Centre), Orange, Australien

13One Clinical Research, Nedlands, Australien

14University of Texas MD Anderson Cancer Center, Houston, USA

15China and BeiGene USA, Inc., San Mateo, USA

16Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Department of

Clinical Haematology, Melbourne, Australien

Background: BCL2, a key apoptosis regulator, is aberrantly expressed

in many hematologic malignancies. e highly selective BCL2 inhibitor,

BGB-11417, demonstrated more potent antitumor activity than vene-

toclax in preclinical studies. Here, preliminary results for BGB-11417 +

azacitidine (aza) in AML are presented.

Methods: BGB-11417-103 (NCT04771130) is an ongoing, phase 1b/2,

global, dose-escalation/expansion study. Eligible pts have treatment

(tx)-naïve (TN) AML (unt for intensive induction chemotherapy) or

relapsed/refractory (R/R) AML (no prior aza or BCL2 inhibitors). Pts

received 40mg (Cohort 1), 80mg (Cohort 2), or 160mg (Cohort 3) BGB-

11417 for 10 d + aza (75 mg/m2 x 7 d). Cycle 1 had a 4-d BGB-11417

ramp-up. Dose-limiting toxicity (DLT) through Day 28 (nonhemato-

logic) and Day 42 (hematologic), tx-emergent AEs, and responses (2017

European LeukemiaNet criteria) were assessed.

Result: As of 10 Jan2022, 27 pts were treated (Cohort 1 n=6; Cohort 2

n=15; Cohort 3 n=6). Median age was 80 y (TN n=18) and 70 y (R/R n=9);

44% had adverse karyotype. At a median follow-up of 2.1 mo and median

tx duration of 1.8 mo (range 0.3-7.6), 2/23 evaluable pts had DLTs: Grade

[Gr]4 neutropenia and Gr4 thrombocytopenia (Cohort 2) which did not

meet safety stopping criteria. 1 pt (Cohort 3) with chronic kidney disease

had asymptomatic laboratory tumor lysis syndrome. e most common

nonhematologic AEs were constipation (37%) and aza injection-site reac-

tion (33%). e most common Gr≥3 hematologic AEs were neutropenia

(44%), thrombocytopenia (41%), and anemia (37%). No pts had BGB-

11417 dose reductions. 10 pts discontinued tx: AEs (n=3), proceeding to

transplant (n=3), withdrawal (n=2), or disease progression (n=2). CR/

CRh rates were 56% (TN) and 44% (R/R). 7/9 CRs occurred by the end

of Cycle 1.

Discussion: Preliminary data suggest that 10-d BGB-11417 + aza was

well-tolerated with promising activity in AML. Most AEs were low-grade

in severity. 2 DLTs were seen across the 3 dose levels tested.

Conclusion: BGB-11417 + aza resulted in a majority of CR by the end of

Cycle 1 and was well-tolerated in AML.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1042

The signicance of BCR-ABL dependent EpCAM expression for

treatment resistance in CML

Tara Towhidi1; Ruimeng Zhuang2; Manfred Jücker2; Vijay Kumar Boddu1;

Oliver Gires3; Hauke Busch4; Lena Illert5; Justus Duyster5; Timo Gemoll6;

Frank Gieseler1; Nikolas von Bubno1; Sivahari Prasad Gorantla1

1Klinik für Hämatologie und Onkologie, UKSH, Lübeck, Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland,

3Ludwig-Maximilians-Universität München, München, Deutschland,

4Institut für experimentelle Dermatologie, UKSH, Lübeck, Deutschland,

5Uniklinik Freiburg , Freiburg im Breisgau, Deutschland,

6Klinik für Chirurgie, UKSH, Lübeck, Deutschland

Background: Although tyrosine kinase inhibitors (TKIs) show a remark-

able clinical response against BCR-ABL mediated chronic myeloid leu-

kemia (CML) 15% of the patients develop a resistance. One of the main

reasons for the failure of TKIs is the protection of leukemic stem cells

(LSCs) in the bone marrow. Understanding the complex signaling mech-

anisms which play a major role in in the protection of LSCs is required to

develop more ecient therapies. With this aim we focused on the role of

cell adhesion molecules playing a major role in CML stem cell interaction

with stromal cells.

Methods: Western Blot, qPCR and FACS were used to identify levels of

cell surface markers in 22 leukemia cell lines. Imatinib and nilotinib were

used to treat cells. A knockdown model was used to determine the func-

tional role of EpCAM in K562 cells.

Result: Analysis of 22 cell lines for the cell surface molecules EpCAM,

CD147 and CD47 demonstrated that BCR-ABL positive CML cells show

a signicantly higher expression of EpCAM. Treatment of K562 and Lama

84 cells with TKIs lead to downregulation of EpCAM expression, while

the TKI resistant T315I variant failed to downregulate EpCAM. In addi-

tion, only K562 and Lama 84 cell displayed the activation of ß-catenin

compared to other leukemia cell lines. We observed EpCAM being pro-

cessed and generating EpICD only in BCR-ABL+ cell lines. Overexpression

of EpCAM and EpICD in K562 cells lead to a strong activation of the

MAPK pathway and enhanced TKI resistance. Finally, downregulation of

EpCAM in K562 cells lead to a decrease in cell proliferation followed by

downregulation ofc-myc andCyclin D.

Discussion: Our results suggest that EpCAM expression is BCR-ABL

Kinase mediated. EpCAM knockdown leads to enhanced sensitivity

against TKIs. Our ongoing in vivo mouse model and gene expression

based functional studies will further delineate the role of EpCAM in the

pathogenesis of CML.

Conclusion: Dual inhibition of BCR-ABL and EpCAM mediated cell sig-

naling might be benecial for CML patients. e role of EpCAM in BCR-

ABL+ CML requires further research.

Reference:

e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts144

Lung Cancer

Best-of-Abstract-Vortrag

817

Comprehensive Proling of Tumor Heterogeneity and Its

Microenvironment in Advanced Non-small Cell Lung Cancer at

Single Cell Resolution

Reinhard Buettner1; Yuanyuan Chen2; Margarete Odenthal1; Nan Fang2;

Caicun Zhou3

1Uniklinik Köln, Köln, Deutschland

2Singleron Biotechnologies, Köln, Deutschland

3Tongji University School of Medicine-Shanghai Pulmonary Medicine Hospital,

Shanghai, China, VR

Background: Lung cancer is a highly heterogeneous disease. Cancer cells

and cells within the tumor microenvironment together determine disease

progression, as well as response to or escape from treatment.

Methods: To map the cell type-specic transcriptome landscape of cancer

cells and their tumor microenvironment in advanced non-small cell lung

cancer (NSCLC), we analyzed 42 tissue biopsy samples from stage III/IV

NSCLC patients by single cell RNA sequencing and presented the large

scale, single cell resolution proles of advanced NSCLCs.

Result: In addition to cell types described in previous single cell studies

of early stage lung cancer, we were able to identify new cell types such

as follicular dendritic cells and T helper 17 cells. Tumors from dierent

patients display large heterogeneity in cellular composition, chromosomal

structure, developmental trajectory, intercellular signaling network and

phenotype dominance.

Discussion: Our study revealed a correlation of tumor heterogeneity with

tumor associated neutrophils, which might help to shed light on their

function in NSCLC.

Conclusion: We were able to analyze 42 biopsies from late-stage NSCLC

patients for scRNAseq, and identied for the rst time the tumor hetero-

geneity and immune microenvironment signatures of late stage NSCLC

patients.

Disclosure Statement: e authors declare no conict of interest.

911

Durvalumab (D) + platinum-etoposide (EP) in 1L extensive-

stage small-cell lung cancer (ES-SCLC): Exploratory analysis of

SCLC molecular subtypes in CASPIAN

Mingchao Xie1; Priti Chugh1; Helen Broadhurst2; Zhongwu Lai1; David

Whitston1; Luis Paz-Ares3; Carl Gay4; Lauren Byers4; Charles M. Rudin5; Ross

Stewart6; J. Carl Barrett1; Yashaswi Shrestha7; Jens Panse8

1AstraZeneca, Waltham, USA

2Plus-Project Ltd, Alderley Park, Vereinigtes Königreich

3Hospital Universitario 12 de Octubre, Madrid, Spanien

4The University of Texas MD Anderson Cancer Center, Houston, USA

5Memorial Sloan Kettering Cancer Center, New York, USA

6AstraZeneca, Cambridge, Vereinigtes Königreich

7AstraZeneca, Gaithersburg, USA

8University Hospital RWTH Aachen, Aachen, Deutschland

Background: In the CASPIAN study 1L D+EP signicantly improved OS

vs EP in pts with ES-SCLC with benet sustained aer >3 years of median

follow-up (HR 0.71; 95% CI 0.60-0.86; p=0.0003; median OS [mOS] 12.9

vs 10.5 mos). 4 SCLC subtypes with distinct therapeutic vulnerabilities

were identied using 2 methods (Rudin et al, 2019; Gay et al, 2021) based

on dierential gene expression. In this exploratory analysis using RNA

sequencing (RNAseq) data from CASPIAN we explored the concordance

between the 2 methods and the association of subtypes with OS.

Methods: Pts with ES-SCLC received 4 cycles of D+EP followed by main-

tenance D or up to 6 cycles of EP. RNAseq data were generated from FFPE

tumor samples collected at screening. Data cuto: Mar 22, 2021.

Results: 57/268 (21.3%) pts in the D+EP arm and 47/269 (17.5%) pts in

the EP arm had RNAseq data (biomarker-evaluable population; BEP). In

BEP the % of pts with WHO PS 1 was slightly higher and the % with

brain metastases slightly lower at baseline vs the ITT population. In BEP

mOS was 11.8 mos in the D+EP arm vs 9.1 mos in the EP arm (HR 0.61;

95% CI 0.40-0.92). Prevalence of neuroendocrine (ASCL1, NEUROD1)

and non-neuroendocrine subtypes (POU2F3, YAP1 [Rudin] or Inamed

[Gay]) was similar in both methods. ASCL1 was more prevalent and

NEUROD1 less prevalent with the Rudin method. Inamed and YAP1

subtypes (11% and 8% prevalence) showed high concordance between

methods. Using either method mOS in the D+EP arm was higher in the

Inamed or YAP1 subtype vs the other 3 subtypes.

Conclusions: Among the 4 subtypes the Inamed/YAP1 subtype showed

the longest OS in the D+EP arm; this may represent a subgroup primed to

respond to immunotherapy. Despite the limited sample size this nding is

consistent with other studies.

Reference: Xie M. et al, AACR 2022

Funding: AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1066

Prospective real-world cohort of immuno-(chemo) therapy

(IO) prior to resection, denitive chemo-radiotherapy (CRT), or

palliative therapy in patients with non-small cell lung cancer

(NSCLC) without a primary curative option

Karoline Lehrach1; Sabine Fallscheer2; Birgit Schwenk2; Sebastian

Kramberg2; Jörn Sträter3; Susanne Eschmann4; Rainer Sätzler1;

Frank Heinzelmann5; Martin Faehling2

1Klinik für Thoraxchirurgie, Klinikum Esslingen, Esslingen am Neckar,

Deutschland

2Klinik für Kardiologie und Pneumologie, Klinikum Esslingen, Esslingen am

Neckar, Deutschland

3Institut für Pathologie, Esslingen am Neckar, Deutschland

4MVZ Nuklearmedizin, Marienhospital, Stuttgart,

5MVZ Strahlentherapie, Klinikum Esslingen, Esslingen am Neckar, Deutschland

Background: Recent trials of IO prior to resection in locally advanced

resectable NSCLC report high rates of pathological response and prom-

ising survival. However, primarily irresectable patients were excluded.

Moreover, there is no data on CRT aer IO in patients who are primar-

ily not amenable to CRT. We hypothesized that induction IO may enable

NSCLC patients with a potentially curative stage including oligomet-

astatic disease (II – IVB [M1b]), for whom primary curative treatment

(resection or CRT) is not possible for anatomical or functional reasons, to

receive curative treatment.

Methods: We enrolled 59 NSCLC patients with aforementioned charac-

teristics into a prospective real-world cohort of induction IO followed by

morphologic and metabolic reassessment and multidisciplinary board-

guided curative treatment (resection [preferred] or CRT) or palliative

therapy. Primary endpoint was the proportion of patients receiving cura-

tive treatment. Results of the rst 35 patients have been published recently

(KOMPASS-neo trial, Faehling (2021), EJC 156:175).

Results: 56 patients (95%) received curative treatment (23 R0 resections,

33 CRT). Of the completely resected patients, 11 had a major pathological

response, including 9 with a pathological complete response. ere were

23 recurrences: 3 (13%) in resected patients, 17 (52%) in CRT-patients,

and 3 (100%) in palliative patients (FU 15 months). 21 deaths occurred

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 145

(15 tumor-related deaths: 12 in CRT patients, and 3 in palliative patients;

2 treatment-related deaths (1 peri-operative, 1 RT pneumonitis); 4 other

causes).

Conclusions: In locally advanced or oligometastatic NSCLC without a

primary curative option, induction IO results in a high rate of curative

treatment with promising early survival data. Resected patients achieved

a high rate of prognostically favorable pathological response.

Disclosure Statement: e authors declare the following: MF is PI in phase 2 – 3

clinical trials by AstraZeneca, BMS, MSD, and Roche, for which payments were

made to my institution. He has received payment for advisory boards and speaker’s

honoraria by AstraZeneca, BMS, MSD, and Roche. Attendance of the virtual

WCLC 2020 was supported by AstraZeneca. SK reports speaker’s honoraria by

Roche.

Poster

Durvalumab ± tremelimumab + chemotherapy as rst-line

treatment for mNSCLC: results from the Phase 3 POSEIDON

study

Jens Kern1; Melissa L. Johnson2; Byoung Chul Cho3; Alexander Luft4;

Jorge Alatorre-Alexander5; Sarayut Lucien Geater6; Konstantin Laktionov7;

Aleksandr Vasiliev8; Sang-We Kim9; Grygorii Ursol10; Maen Hussein11;

Farah Louise Lim12; Cheng-Ta Yang13; Luiz Henrique Araujo14;

Haruhiro Saito15; Niels Reinmuth16; Xiaojin Shi17; Lynne Poole18;

Nenad Medic18; Solange Peters19; Edward B Garon20; Tony Mok21;

Michael Thomas22

1Standort Missioklinik, Klinikum Würzburg Mitte gGmbH, Würzburg,

Deutschland

2Sarah Cannon Research Institute, Nashville, USA

3Yonsei Cancer Center, Seoul, Republik Korea

4Leningrad Regional Clinical Hospital, St. Petersburg, Russische Föderation

5Health Pharma Professional Research, Mexico City, Mexiko

6Prince of Songkla University, Songkhla, Thailand

7Federal State Budgetary Institution “N.N. Blokhin National Medical Research

Center of Oncology” of the Ministry of Health of the Russian Federation (N.N.

Blokhin NMRCO), Moskau, Russische Föderation

8“Private Health Institution “Clinical Hospital” RZD-Medicine”, St. Petersburg,

Russische Föderation

9Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republik

Korea

10Acinus, Kropyvnytskyi, Ukraine

11Florida Cancer Specialists – Sarah Cannon Research Institute, Leesburg, USA

12Queen Mary University of London, London, Vereinigtes Königreich

13Chang Gung Memorial Hospital, Taoyuan City, Taiwan

14Instituto Nacional de Cancer-INCA, Rio de Janeiro, Brasilien

15Kanagawa Cancer Center, Yokohama, Japan

16Asklepios Lung Clinic, Munich-Gauting, Deutschland

17AstraZeneca, Gaithersburg, USA

18AstraZeneca, Cambridge, Vereinigtes Königreich

19Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne,

Schweiz

20David Geen School of Medicine at UCLA, Los Angeles, USA

21Chinese University of Hong Kong, Hong Kong, China, VR

22Thoraxklinik Heidelberg gGmbH , Universitätsklinikum Heidelberg, Heidelberg,

Deutschland

Introduction: Immunotherapies targeting the PD-1/PD-L1 pathway

have transformed the treatment of metastatic NSCLC (mNSCLC) as

monotherapy and in combination with chemotherapy (CT). POSEIDON

(NCT03164616) is a randomized, open label, global phase 3 study evalu-

ating durvalumab (D) ± tremelimumab (T) in combination CT regimens

as 1L treatment for squamous or non-squamous mNSCLC.

Methods: Patients (pts) with treatment-naïve, EGFR/ALK wildtype mNS-

CLC were randomized (1:1:1) to receive: D 1500 mg + CT q3w for 4 cycles

followed by D 1500 mg q4w until progression; D 1500 mg + T 75 mg with

CT q3w for up to 4 cycles, followed by D 1500 mg q4w until progres-

sion, with one additional dose of T post CT; or CT q3w for up to 6 cycles.

Primary endpoints were PFS by BICR and OS for D+CT versus CT, posi-

tivity for either of which triggered analysis of the key secondary endpoints

PFS by BICR and OS for D+T+CT versus CT. Global health status/QoL,

functioning and symptoms were assessed using EORTC QLQ-C30/LC13.

Results: 1013 pts were randomized. 28.8% had PD-L1 TC 50%, 49.6% had

stage IVB disease, and 36.9% had squamous histology. PFS was signi-

cantly improved with D+CT versus CT, with a trend for OS improvement

that did not reach statistical signicance. Both OS and PFS were statisti-

cally signicantly improved with D+T+CT versus CT. e incidence of

Grade 3/4 treatment-related AEs (TRAEs) was 44.6%, 51.8%, and 44.4%

with D+CT, T+D+CT and CT, respectively, and 14.1%, 15.5% and 9.9% of

patients had TRAEs leading to any study treatment discontinuation. Pts in

the D+CT and T+D+CT arms tended to have longer time to deterioration

and greater rates of improvement in global health status/QoL, functioning

and symptoms vs pts in the CT arm.

Conclusion: D+T+CT demonstrated statistically signicant improve-

ments in both PFS and OS versus CT in pts with mNSCLC. Overall, the

safety prole was similar across all three arms, with no new safety signals

identied; treatment discontinuation rates were similar with D+CT and

T+D+CT.

Reference:

Johnson, M. et al, WCLC 2021, LBA #833 and Garon, EB. Et al, ELCC 2022 #243

Funding: AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Atezolizumab (atezo) vs best supportive care (BSC)

in stage II-IIIA NSCLC with high PD-L1 expression:

sub-analysis from the pivotal phase III IMpower010 study

Enriqueta Felip1; Nasser Altorki2; Caicun Zhou3; Eric Vallieres4;

Ihor Vynnychenko5; Andrey Akopov6; Alex Martinez-Marti1;

Antonio Chella7; Igor Bondarenko8; Grygorii Ursol9; Evgeny Levchenko10;

Nikolay Kislov11; Rüdiger Liersch12; Rossella Belleli13; Virginia Mcnally14;

Elizabeth Bennett15; Barbara Gitlitz15; Heather Wakelee16

1Vall d’Hebron Institute of Oncology , Vall d’Hebron University, Barcelona,

Spanien

2Weill Cornell Medicine, New York, USA

3Tongji University Aliated Shanghai Pulmonary Hospital, Shanghai, China, VR

4Swedish Cancer Institute, Seattle, USA

5Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary,

Sumy State University, Sumy, Ukraine

6Pavlov State Medical University, Saint Petersburg, Russische Föderation

7Azienda Ospedaliero Universitaria Pisana, Pisa, Italien

8Dnipro State Medical University, Dnipro, Ukraine

9Acinus, Kropyvnytskyi, Ukraine

10N.N. Petrov National Medical Research Center of Oncology, St Petersburg,

Russische Föderation

11Regional Clinical Oncology Hospital, Yaroslavl, Russische Föderation

12Clemenshospital Münster, Münster, Deutschland

13F. Homann-La Roche Ltd, Basel, Schweiz

14Roche Products Ltd, Welwyn Garden City, Vereinigtes Königreich

15Genentech Inc., South San Francisco, USA

16Stanford Cancer Institute, Stanford, USA

Background: IMpower010 showed signicant DFS benet with atezo aer

adjuvant chemo in resected NSCLC (Felip Lancet 2021). At the interim

DFS analysis, the signicance boundary was crossed for the stage II-IIIA

PD-L1 TC≥1% population (stratied HR, 0.66; 95% CI: 0.50, 0.88), with

greatest benet in the PD-L1 TC≥50% subgroup (unstratied HR, 0.43;

95% CI: 0.27, 0.68). Here we present further analyses in PD-L1 TC ≥50%

stage II-IIIA NSCLC pts.

Methods: IMpower010 (NCT02486718) study design and primary DFS

analysis details have been reported (Felip Lancet 2021). DFS in PD-L1

TC ≥50% (VENTANA SP263) stage II-IIIA (UICC/AJCC v7) pts was a

prespecied secondary endpoint; additional subgroup data reported are

exploratory.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts146

Result: Baseline characteristics were generally balanced for atezo- vs BSC-

arm pts with PD-L1 TC ≥50% stage II-IIIA NSCLC. Median follow-up

was 34.2 mo (21 Jan 2021 cuto). Pts beneted throughout most sub-

groups including squamous (HR, 0.60; 95% CI: 0.29, 1.26) and nonsqua-

mous (HR, 0.36; 95% CI: 0.20, 0.65) histology; stage II (HR, 0.51; 95%

CI:0.26, 1.00) and stage IIIA (HR, 0.38; 95% CI: 0.20, 0.72); N1 (HR, 0.29;

95% CI: 0.12, 0.72) and N2 (HR, 0.35; 95% CI: 0.18, 0.68) status. Safety in

PD-L1 TC≥50% stage II-IIIA pts was consistent with that of the overall

population and known safety prole of atezo. Initial disease relapse was

locoregional-only in 15/25 atezo-arm pts (60%) vs 17/50 BSC-arm pts

(34%) and distant-only in 6/25 (24%) vs 21/50 (42%); CNS-only relapse

was seen in 1/25 (4%) vs 7/50 (14%).

Discussion: Data from other randomised phase 3 adjuvant studies of

PD-1/PD-L1 inhibitors will further elucidate the role of CIT in the adju-

vant setting in eNSCLC.

Conclusion: IMpower010 pts with PD-L1 TC≥50% stage II-IIIA NSCLC

derived DFS benet with atezo vs BSC at the interim DFS analysis. Data

were consistent across most subgroups, albeit with limited pt numbers in

this post hoc analysis. Numerically, more distant and CNS relapses were

seen with BSC. e tolerability prole of atezo was in line with the overall

population, demonstrating a positive benet-risk prole.

Disclosure Statement: e authors declare the following: Honorare von AbbVie,

Astra Zeneca, BMS, Boehringer Ingelheim, Daichi Sankyo, Eli Lilly, MSD, Novar-

tis, Pzer, Roche

Clinical observation after combined pulmonary Stereotactic

Radiotherapy (SBRT) and mediastinal conventionally

fractionated Volumetric Arc Therapy (VMAT) in advanced

Non-Small Cell Lung Cancer (NSCLC)

Cedric Stüwe1,2; Tanja Eichkorn1,2; Eric Tonndorf-Martini1,2; Kai Schubert1,2;

Sebastian Regnery1,2; Thomas Held1,2; Farastuk Bozorgmehr3,4;

Petros Christopoulos3,4; Laila König1,2; Patrick Naumann1,2;

Sebastian Adeberg1,2; Klaus Herfarth1,2; Michael Thomas3,4; Stefan Rieken5;

Jürgen Peter Debus1,2,4,6 7; Rami A. El Shae5

1Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg,

Deutschland

2National Center for Radiation Oncology (NCRO), Heidelberg Institute for

Radiation Oncology (HIRO), Heidelberg, Deutschland

3Thoracic Clinic, Heidelberg University, Heidelberg,

4National Center for Tumor diseases (NCT), Heidelberg University, Heidelberg,

Deutschland

5Department of Radiation Oncology, Göttingen University Hospital, Göttingen,

Deutschland

6Clinical Cooperation Unit Radiation Oncology (E050), German Cancer Research

Center (DKFZ), Heidelberg, Deutschland

7Deutsches Konsortium für Translationale Krebsforschung (DKTK), German

Cancer Research Center (DKFZ), Heidelberg, Deutschland

Background: Rates for pneumonitis in radiotherapy of the lung dif-

fer widely depending on the irradiated lung volume and dose exposure.

Other factors such as chemotherapy, or pulmonary diseases are shown to

further increase pneumonitis rates. In patients with peripherally located

advanced stage Non-small Cell Lung Cancer, large target volumes or

pre-existing pulmonary conditions can necessitate dose reductions to

reduce toxicity.

Methods: 21 patients with stage III or oligometastatic stage IV NSCLC

with peripherally located primary where a single target volume resulted

in clinically unacceptable dose exposure of the lungs were treated with

denitive radio(chemo)therapy using conventionally fractionated medi-

astinal volumetric arc radiotherapy (VMAT) in combination with stereo-

tactic radiotherapy (SBRT) for the primary. Patients were retrospectively

observed for a median of 2.7 years (range: 2.4 months - 5,8 years) using

medical and ocial records.

Results: Median patient age was 63.3 years (IQR 56-73). 85% of patients

received simultaneous or sequential platinum-based chemotherapy.

Median overall survival and median progression-free survival were 3.4

years (range: 2.4 months - 5.8 years) and 1.2 years (range: 1 month - 5.2

years), respectively. Median intrathoracic progression-free survival and

median primary tumor progression-free survival were not reached during

the follow-up period. In two cases (10%), pneumonitis occurred with one

being graded as CTCAE grade 1 and one being graded as CTCAE grade 3.

Grade 3 pneumonitis was treated with corticosteroids and antibiotics and

grade I pneumonitis remitted without further treatment.

Discussion: Pneumonitis probability seems to be reduced without impair-

ments in tumor control with this tissue-sparing radiotherapy approach.

Conclusion: Conventionally fractionated mediastinal VMAT in combina-

tion with SBRT for the primary is feasible and could reduce pneumonitis

rates in a patient cohort unsuitable for the conventional radiotherapy due

to otherwise large target volumes or pre-existing pulmonary conditions.

Disclosure Statement: e authors declare no conict of interest.

Neoadjuvant Osimertinib with/without Chemotherapy

vs Chemotherapy for EGFR Mutated Resectable NSCLC:

NeoADAURA

Frank Griesinger1; Masahiro Tsuboi2; Walter Weder3; Carles Escriu4,

Collin Blakely5; Jianxing He6; Sanja Dacic7; Yasushi Yatabe8,

Lingmin Zeng9; Andrew Walding10; Jamie Chaft11

1Pius-Hospital Oldenburg, Oldenburg, Deutschland

2National Cancer Center Hospital East, Kashiwa, Japan

3Department of Thoracic Surgery, Thoraxchirurgie, Klinik Bethanien, Zürich,

Schweiz

4The Clatterbridge Cancer Centre, Bebington, Wirral, Vereinigtes Königreich

5Department of Medicine, University of California, San Francisco, CA, USA

6The First Aliated Hospital Of Guangzhou Medical University, Guangzhou,

China, VR

7Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh,

PA, USA

8Department of Diagnostic Pathology, National Cancer Center, Tokyo, Japan

9Late Oncology Statistics, AstraZeneca, Gaithersburg, MD, USA

10AstraZeneca R&D, Alderley Park, Vereinigtes Königreich

11Memorial Sloan Kettering Cancer Center, New York, NY, USA

Background: Ca. 30% of NSCLC patients present in resectable stages.

Prim. treatment is curative surgery; prognosis aer surgery alone remains

poor. Neoadj. chemo. is recommended in resectable St. III NSCLC, regard-

less of EGFR status, and has shown clinical benet. Recent studies indicate

that EGFR-TKI could potentially reduce tumor size and clear microme-

tastases before surgery. Osimertinib is a 3rd-Gen., CNS-active EGFR-TKI,

with superior ecacy to other EGFR-TKIs in treatment-naïve EGFRm

adv. NSCLC. In the Ph. III ADAURA trial (NCT02511106), osimertinib

showed sig. DFS improvement (HR: 0.20 [99.12% CI 0.14, 0.30; p<0.001)

in resected IB-IIIA EGFRm NSCLC following adj. chemo, if indicated.

NeoADAURA (NCT04351555) is a Ph. III, controlled, randomized study

assessing ecacy and safety of osimertinib (+/- chemo) vs chemo + pla-

cebo as neoadj. treatment in resectable St. II-IIIB EGFRm NSCLC.

Methods: Eligible pts: ≥18 yrs (≥20 yrs, Japan), ECOG PS 0/1, prim.

non-sq. St. II-IIIB (IASLC Cancer Staging Manual v8) NSCLC and con-

rmed EGFRm, deemed completely resectable. No prior treatment with

systemic therapy for NSCLC is allowed. Ca. 351 pts will be randomized

1:1:1 to receive platinum-based chemo (pemetrexed 500 mg/m2 + car-

boplatin AUC5 or cisplatin 75 mg/m2) + placebo (Arm 1; double-blind),

platinum-based chemo + osimertinib 80 mg QD (Arm 2; double-blind)

or osimertinib 80 mg QD alone (Arm 3; open-label). Pts will be stratied

by disease St. (II/III), race (non-Asian/Chinese/other Asian) and EGFR

mutation (Ex19del/L858R). Following 3 cycles of chemo (Arms 1 and 2)

or 9 weeks of osimertinib (Arm 3), pts will undergo surgical resection of

prim. NSCLC. Treatment with osimertinib or placebo may continue until

surgery. Post-surgery, pts will receive optimal care (investigator-dened);

this may include adj. osimertinib treatment for 3 yrs (max.)/until recur-

rence or unmanageable toxicity. Prim. endpoint is MPR (≤10% residual

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 147

cancer cells in surgical specimen). Secondary endpoints: pCR, EFS, down-

staging, DFS, OS, safety.

Originally presented at WCLC 2020

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Patterns of pretreatment diagnostic assessment in patients

treated with stereotactic body radiotherapy (SBRT) for

non-small cell lung cancer (NSCLC): special characteristics

in the COVID-19 pandemic and inuence of parameters on

outcomes

Felix-Nikolai Oschinka Jegor Habermann1,2; Daniela Schmitt1,2;

Thomas Failing1,2; Jann Fischer1,2; Sandra Donath1,2;

Markus Anton Schirmer1,2; Manuel Guhlich1,2; Niklas Josua Alt1,2;

Julian Muster1,2; Rami El Shae1,2; Stefan Rieken1,2; Martin Leu1,2;

Leif Hendrik Dröge1,2

1Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,

Göttingen, Deutschland

2University Medical Center Göttingen, Comprehensive Cancer Center

Niedersachsen, Göttingen, Deutschland

Background: e pandemic raised a discussion about postponement of

medical interventions for lung cancer. We analyzed the special charac-

teristics of pretreatment diagnostic assessment in the pandemic and the

inuence of diagnostic assessment on outcomes.

Methods: A total of 96 patients with stereotactic body radiotherapy

(SBRT) for non-small cell lung cancer (NSCLC) were included. We com-

pared characteristics in the pre-COVID era (2012-2019) and characteris-

tics in the COVID era (2020-2021). We analyzed whether pretreatment

diagnostic assessment and the time from assessment to SBRT initiation

had an inuence on outcomes.

Results: e number of patients per month with SBRT was higher in the

COVID era (mean 1.5) than in the pre-COVID era (mean 0.9) (p=0.04).

In the COVID era, we found longer times from the planning CT scan to

the initiation of SBRT (p<0.001, mean, 3.0 vs. 1.7 weeks). Patients who

received a pretreatment PET/CT scan (n=83) experienced better overall

survival (p=0.02, 2 years, 61% vs. 29%) than patients who underwent

conventional staging (n=13). A longer time from the PET/CT scan to the

initiation of SBRT (<10 vs. ≥10 weeks) was associated with worse locore-

gional control (p=0.01, 2 years, 97% vs. 70%).

Discussion: e pandemic raised the question whether medical interven-

tions can safely be postponed. At the same time, patients are at risk of

tumor progression. Lung SBRT can be performed as an outpatient pro-

cedure with less close contacts. e preference to refer patients to SBRT

might explain the increase in patients treated in the COVID era. e lon-

ger times from the planning CT scan to SBRT might reect the eorts to

slow the virus spread. Our study points out that eorts should be made to

obtain a PET/CT scan close to SBRT.

Conclusion: e ndings on special characteristics of management

during the COVID era might serve as a basis to guide strategies in similar

future scenarios. e postponement of interventions should be carefully

discussed with consideration of an accurate and timely staging workup.

Disclosure Statement: e authors declare no conict of interest.

Predictive value of mRNA expression and dynamic changes

from immune related biomarkers in liquid biopsies before and

after start of pembrolizumab in stage IV non-small cell lung

cancer (NSCLC)

Natalie Brückl1; Ralph Wirtz2; Elke Veltrup2; Christian Meyer3;

Gloria Zeitler4; Dieter Wuerein4; Fabian Reich4; Joachim Ficker4;

Sebastian Eidt1; Wolfgang Brückl4

1Institut für Pathologie, St. Elisabeth Krankenhaus Köln, Lehrkrankenhaus

Universität Köln

2Institut für Pathologie, St. Elisabeth Krankenhaus Köln, STRATIFYER Molecular

Pathology GmbH, Köln

3Institut für Pathologie, Klinikum Nürnberg, Paracelus Medizinische

Privatuniversität (PMU) Standort Nürnberg, Nürnberg

4Medizinische Klinik 3, Klinikum Nürnberg, Paracelus Medizinische

Privatuniversität (PMU) Standort Nürnberg, Nürnberg

Background: e aim of this study was to determine whether mRNA

expressions and dynamic changes of immune-related genes before and

aer starting rst-line treatment with the PD-1 inhibitor pembrolizumab

in patients with NSCLC were of predictive value.

Methods: CD3, CD8, PD-1, PD-L1 and CTLA-4 mRNA expression lev-

els were measured from peripheral blood before and aer three weeks

of treatment with the PD-1 inhibitor. Univariate and multivariate anal-

yses were performed retrospectively. Response, progression-free survival

(PFS) and overall survival (OS) were determined.

Results: In univariate analysis an increase of CD3 and CD8 mRNA

expression aer the rst cycle of pembrolizumab were each associated

with improved PFS and OS. In contrast, patients with no change or with a

decrease in CD3 and CD8 mRNA expression showed signicantly worse

outcome. CD8 mRNA increase remained an independent prognostic fac-

tor for PFS and OS in the multivariate analysis with p values of 0.011 and

0.006, respectively.

Conclusion: An increase of CD8 mRNA expression predicts favorable

outcome aer rst line monotherapy with pembrolizumab, while no

change or decrease might serve as an indicator of poor outcome and

might give cause for early treatment escalation for instance by addition of

chemotherapy or additional ICI treatment e.g. against CTLA-4.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

116

Durvalumab ± tremelimumab + platinum-etoposide in rst-

line extensive-stage SCLC (ES-SCLC): 36-monthoverall survival

from the Phase 3 CASPIAN study

Luis Paz-Ares1; Christian Schulz2

1Department of Medical Oncology, Madrid, Spanien

2University Hospital Regensburg, Regensburg, Deutschland

Background: Etoposide plus either cisplatin or carboplatin (EP) had been

the standard rst-line (1L) treatment for ES-SCLC, with limited alter-

native therapies for more than three decades, until recent progress with

immunotherapy in this setting. e Phase 3, randomised, open-label,

global CASPIAN study assessed EP ± durvalumab (D) ± tremelimumab

(T) as 1L treatment for patients with ES-SCLC, and D + EP demonstrated

a statistically signicant improvement in overall survival (OS) compared

with EP alone (data cut-o [DCO]: March 11, 2019): HR 0.73 (95% CI

0.59–0.91; p=0.0047). Aer a median follow-up of 25.1 months (DCO

Jan 27, 2020), the OS benet with D + EP vs EP was sustained (HR 0.75

[95% CI 0.62–0.91; nominal p=0.0032]), and D + T + EP numerically

improved OS vs EP (HR 0.82 [95% CI 0.68–1.00; p=0.0451]), but did not

reach statistical signicance (p≤0.0418) per prespecied statistical plan.

At 24 months, 22.2% of patients were alive in the D+ EP arm, 23.4% in

the D + T + EP arm, and 14.4% in the EP arm. Here we report updated

OS data from the CASPIAN study, aer a median follow-up of approx.

36months.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts148

Methods: In the CASPIAN study, 805 patients with treatment-naïve

ES-SCLC (WHO performance status 0/1) were randomised 1:1:1 to D

1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w, stratied

by planned platinum (investigator’s choice of carboplatin or cisplatin).

Patients in the immunotherapy arms received 4 cycles of EP + D ± T, fol-

lowed by maintenance D 1500 mg q4w until disease progression. Patients

in the D + T+ EP arm received an additional dose of T 75 mg aer EP.

Patients in the EP arm received up to 6 cycles of EP in total, and optional

prophylactic cranial irradiation at the investigator’s discretion. e two

primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP.

Result: We present mature OS data for patients in the CASPIAN study,

based on a median follow-up duration of approx. 36 months.

Conclusion: is updated analysis of OS from the CASPIAN trial will

provide further insight into long-term survival benet with D + EP and D

+ T + EP vs EP in 1L treatment of patients with ES-SCLC.

Funded by AstraZeneca.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

135

Clinical Research platform Into molecular testing, treatment

and outcome of non-Small cell lung carcinoma Patients

(CRISP): First Real-World Evidence of NSCLC Stage II and III in

Germany - AIO-TRK-0315

Andreas Gröschel1; Bernward Passlick2; Martin Stuschke3;

Petros Christopoulos4; Martin Reck5; Christian Grah6; Annika Groth7;

Annette Hipper7; Marco Chiabudini8; Annette Fleitz8; Martina Jänicke8;

Lisa Spring8; Daniel Christoph9; Christiane Bernhardt10; Marcel Reiser11;

M.-O. Zahn12; Martin Sebastian13; Frank Griesinger14; Michael Thomas4;

Wilfried Eberhardt15

1Clemenshospital Münster, Klinik für Innere Med. II - Pneumologie und

Beatmungsmedizin, Münster, Deutschland

2Uniklinik Freiburg - Klinik für Thoraxchirurgie, Freiburg im Breisgau,

Deutschland

3Universitätsklinikum Essen, Westdeutsches Tumor Zentrum, Strahlenklinik,

Essen, Deutschland

4Thoraxklinik-Heidelberg, National Center for Tumor Diseases at Heidelberg

University Hospital, Translational Lung Research Center Heidelberg (TLRC-H),

member of the German Center for Lung Research (DZL), Heidelberg,

Deutschland

5LungenClinic Grosshansdorf, Großhansdorf, Deutschland

6Gemeinschaftskrankenhaus Havelhöhe , Klinik für Anthroposophische Medizin,

Berlin, Deutschland

7AIO-Studien-gGmbH, Berlin, Deutschland

8iOMEDICO, Freiburg im Breisgau, Deutschland

9MVZ für Hämatologie und Onkologie Essen gGmbH, Essen, Deutschland

10Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Deutschland

11PIOH - Praxis Internistische, Onkologie und Hämatologie, Köln, Deutschland

12Überörtliche Berufsausübungsgemeinschaft, MVZ Onkologische Kooperation,

Goslar, Deutschland

13Universitätsklinikum Frankfurt, Medizinische Klinik 2 Hämatologie/Onkologie,

Frankfurt am Main, Deutschland

14Pius-Hospital Oldenburg, Klinik für Hämatologie und Onkologie, Oldenburg,

Deutschland

15Ruhrlandklinik, Westdeutsches Lungenzentrum, Essen, Deutschland

Background: CRISP is a non-interventional, prospective, multi-center

clinical research platform whose aim is to understand the treatment real-

ity of patients (pts) with lung cancer in Germany. Here we present data of

pts diagnosed with early-stage NSCLC.

Methods: Since August 2018 106 sites in Germany have recruited about

1400 pts diagnosed with NSCLC stage I-III. Basic demographic data,

details about treatment reality, outcome and PRO data are collected and

analyzed. Here we show data on the rst 810 pts followed until June 2021.

Results: 26% of pts were diagnosed with stage II (5% stage IIA, 21% stage

IIB), 66% with stage III (32% stage IIIA, 34% stage IIIB/C).

Characteristics at diagnosis were: median age 66 years, 38% female, 83%

ECOG 0/1, 80% with comorbidities, 47% Charslon Comorbidity Index

of 0; 25% current smokers; 44%, heavy ex-smokers, 9% never-smokers.

Most of pts with tumors in clinical stage II underwent surgery (84%,

n=157) followed by adjuvant chemotherapy (CTx) (75%, n=140). e

2-year relapse-free survival (RFS) rate was 77% and the 2-year overall sur-

vival (OS) rate was 90%.

For pts with clinical stage IIIA tumors the most frequent treatment strat-

egy was also surgery (53%, n=124) followed by adjuvant CTx (37%, n=88);

the 2-year RFS rate was 52%, and the 2-year OS rate was 79%. 27% (n=64)

of pts with stage IIIA received denitive radiochemotherapy (RTCTx).

For pts with stage IIIB/C tumors the most frequent treatment was deni-

tive RTCTx (n=131, 53%); 26% (n=64) started with CTx, and 18% (n=44)

had surgery (followed mostly by CTx, n=36, 15%).

80% (n=131) of pts with an inoperable stage III tumor who received

RTCTx were tested for PD-L1 expression. 80 pts had a positive PD-L1

expression. 44 pts out of 68 eligible (best response CR/PR/SD) received

consolidation therapy with durvalumab.

Conclusion: CRISP presents comprehensive current real-life data of

patients with NSCLC in stage II or III covering all treatment settings in

Germany. With a longer recruitment time data on patients with stage I

will be analyzed.

Indication of source: ESMO Congress 2021 (data updated)

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

209

Breaking the crosstalk of the Cellular Tumorigenic Network in

NSCLC by a highly eective drug combination

Dennis Gürgen1; Theresia Conrad1; Michael Becker1; Susanne Sebens2;

Christoph Röcken3; Jens Homann1; Stefan Langhammer4

1EPO Experimental Pharmacology & Oncology GmbH, Berlin, Deutschland

2Institute for Experimental Cancer Research, Kiel University and University

Hospital Schleswig-Holstein, Campus Kiel, Kiel, Deutschland

3Institute for Pathology, Kiel University, Kiel, Deutschland

4life science consulting, Burgwedel, Deutschland

Background: Non-small cell lung cancer (NSCLC) is commonly diag-

nosed at advanced stages with limited treatment options particularly in

tumors without targetable driver mutations.

Methods: Considering previously published criteria for selecting drug

combinations for overcoming drug resistances, we have established a low

dose combination therapy with cabozantinib, afatinib, etoricoxib and

plerixafor. Utilizing NSCLC patient-derived xenogra (PDX) models we

aimed to use this drug regimen to disrupt paracrine substitutional sig-

naling within the Cellular Tumorigenic Network in order to circumvent

pre-existing and adaptive drug resistances.

Result: All PDX tumors treated, including highly therapy-resistant adeno-

and squamous cell carcinomas without identiable driver mutations,

were completely suppressed by this drug regimen leading to an Objective

Response Rate of 81% and a Clinical Benet Rate of 100%. Aer treat-

ment discontinuation growth suppression remained until the end of the

follow-up period with only slight increase in tumor growth. e applica-

tion and the safety prole of this low dose therapy regimen was well man-

ageable and without pronounced side eects in this pre-clinical setting.

Discussion: For the rst time we show that simultaneous inhibition of

pathways forming the Cellular Tumorigenic Network in NSCLC tumors

is highly eective and overcomes drug resistances for monotherapies. All

of the drugs used in this combination regimen are approved for dierent

indications and therefore readily available.

Conclusion: Our results emphatically encourage a setup for a clinical

study in advanced stage NSCLC patients without targetable driver muta-

tions combining the drugs cabozantinib, afatinib, plerixafor and etoricoxib

in a low dose treatment regimen as novel therapy strategy.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 149

Indication of Source: Gürgen et al. Breaking the crosstalk of the Cellular

Tumorigenic Network by low-dose combination therapy in lung cancer

patient-derived xenogras.Commun Biol. 5:59, 2022.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

218

Early circulatingtumourDNA (ctDNA) dynamics for

predicting and monitoring response to immunotherapy(IO) vs

chemotherapy (CT) in patients with 1L metastatic (m) NSCLC:

analyses from the Phase 3 MYSTIC trial

S. Peters1; N. Rizvi2; M. Kuziora3; Z. Lai4; Y. Shrestha3; A. Dey5; J.C. Barrett3;

U. Scheuring6; L. Poole7; C. Abbosh8; R. Raja3; M. Hellmann9; J. Panse10

1Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University,

Department of Oncology, Lausanne, Schweiz

2Columbia University Medical Center, Division of Hematology/Oncology,

NewYork, USA

3AstraZeneca, Translational Medicine, Gaithersburg, USA

4AstraZeneca, Translational Medicine, Waltham, USA

5AstraZeneca, Clinical Pharmacology and Quantitative Pharmacology,

Waltham,USA

6AstraZeneca, Global Medicines Development, Cambridge, Vereinigtes

Königreich

7AstraZeneca, Biostatistics, Cambridge, Vereinigtes Königreich

8University College London Cancer Institute, Cancer Research UK Lung Cancer

Centre of Excellence, London, Vereinigtes Königreich

9Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service, Division of

Solid Tumor Oncology, Department of Medicine, New York, USA

10Uniklinik RWTH Aachen, Oncology, Hemostaseology and Stem Cell

Transplantation, Aachen, Deutschland

Background: We have previously shown that ctDNA dynamics can

identify pts as “molecular responders” (MRs) to IO who have improved

OS compared with molecular non-responders (non-MRs). Larger ran-

domized studies in specic clinical settings including 1L are needed to

optimize use of ctDNA as a biomarker of response. We report analyses

of ctDNA in pts with mNSCLC treated with 1L durvalumab (D), D +

tremelimumab (T), or CT in the phase 3 MYSTIC trial.

Methods: Plasma was collected at baseline (BL) and on-treatment (pre-

dose at cycle 2 of D ± T/cycle 3 of CT) and ctDNA was sequenced using

the Guardant OMNI panel (500 genes). Mean variant allelic frequency

(VAF) values of BL variants with ≥ 0.3% VAF and the change between BL

and on-treatment were used to calculate delta VAF. MRs were dened as

having a decrease of ≥ 50% from BL mean VAF.

Results: Biomarker evaluable populations (BEPs) with variants ≥0.3%

VAF were n=901 for BL (BEP1) and n=713 for BL + on-treatment (BEP2).

Both BEPs were similar to the ITT population. Pts with BL mean VAF <

median had longer OS/PFS vs ≥ median in all arms. MRs had longer OS vs

non-MRs with D (HR 0.41, 95% CI 0.28–0.6) and D + T (0.37, 0.26–0.53)

but not CT (1.1, 0.84–1.5); PFS results were similar. At wk 6, MRs had

higher partial response (PR) rates vs non-MRs with D (odds ratio [OR]

4.4, 95% CI 1.7–11.6), D + T (8.7, 3.4–25.5), and CT (8.0, 2.7–32.2); the %

of PD was lower among MRs vs non-MRs with D ± T but not CT. Among

radiologic responders (PR/complete response by BICR), MRs were more

likely to achieve durable response (>6 months) vs non-MRs with D (OR

4.4, 95% CI 2.1–9.4) and D + T (6.8, 3.2–15.2) with a weaker trend for CT

(2.9, 0.91–12.5). Among pts with SD at wk 6, MRs had longer OS vs non-

MRs with D (HR 0.51, 95% CI 0.31–0.86) and D + T (0.58, 0.36–0.94) but

not CT (1.2, 0.83–1.7).

Conclusions: Results indicate that BL ctDNA level is prognostic in 1L

mNSCLC; further, MR is predictive of clinical benet with IO but not CT.

On-treatment ctDNA dynamics may have important predictive value for

long-term outcomes with IO, complementing radiologic assessment and

enabling early decision-making.

Funding: AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

255

Durability of Ecacy with Selpercatinib in Patients (pts) with

RET Fusion+ Non-Small-Cell Lung Cancer (NSCLC)

Alexander E. Drillon1; Vivek Subbiah2; Oliver Gautschi3; Pascale Tomasini4;

Filippo G. De Braud5; Benjamin Solomon6; Daniel Shao-Weng Tan7;

Guzman Alonso8; Juergen Wolf9; Keunchil Park10; Koichi Goto11;

Victoria Soldatenkova12; Sylwia Szymczak12; Scott S. Barker12; Tarun Puri12;

Aimee K. Lin12; Herbert Loong13; Benjamin Besse14

1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College,

NewYork, USA

2Department of Investigational Cancer Therapeutics, The University of Texas MD

Anderson Cancer Center, Houston, USA

3University of Berne and Cantonal Hospital of Lucerne, Lucerne, Schweiz

4Hôpitaux Universitaires, de Marseille Timone, Marseille, Frankreich

5Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei

Tumori, Milan, Italien

6Department of Medical Oncology and Research Division, Peter MacCallum

Cancer Centre and the Sir Peter MacCallum Department of Oncology, University

of Melbourne, Melbourne, Australien

7National Cancer Center, Singapore, Singapur

8Vall d’ Hebron Institute of Oncology (VHIO), Vall d’ Hebron Hospital Universitari,

Barcelona, Spanien

9Department of Internal Medicine, Center for Integrated Oncology, University

Hospital Cologne, Cologne, Deutschland

10Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan

University School of Medicine, Seoul, Republik Korea

11National Cancer Center Hospital East, Kashiwa, Japan

12Eli Lilly and Company, Indianapolis, USA

13Chinese University of Hong Kong, Hongkong, China, VR

14Gustave Roussy Universite’ Paris Sud, Paris, Frankreich

Background: Selpercatinib is approved in multiple countries for treat-

ment of RET fusion+ NSCLC.

Methods: Updated analysis of selpercatinib in pts with RET fusion+

NSCLC in LIBRETTO-001 was conducted with a 15-month (mo) inter-

val between preceding and current analyses. Primary endpoint: ORR by

IRC. Secondary endpoints included DoR, PFS, clinical benet rate (CBR;

CR+PR+SD≥16 weeks), OS and safety.

Result: Ecacy results for treatment naïve pts (N=69) are: ORR%

(95%CI)=84.1 (73.3–91.8) and CBR% (95%CI)=92.8 (83.9–97.6); ecacy

results for pts previously treated with platinum chemotherapy (N=247) are:

ORR% (95%CI)= 61.1(54.7–67.2) and CBR% (95%CI)=85.4(80.4–89.6).

Despite a median follow-up (f/u) of ~24 mo in the treatment naïve and

platinum chemotherapy pretreated populations, median DoR (mDoR)

and PFS(mPFS) estimates are still not mature. Among all NSCLC pts,

26 had measurable CNS metastases at baseline per IRC. Selpercatinib

treatment resulted in a CNS ORR=84.6%(95%CI=65.1–95.6), (CNS

mDoR=9.4 mo [95%CI=7.4–15.3] at a median follow-up [f/u]=25.8 mo).

safety population (NSCLC pts with ≥1 dose, N=356), most common AEs

in ≥25% pts: dry mouth, diarrhea, hypertension, increased ALT/AST,

peripheral edema, constipation, rash, headache, fatigue. 34 pts discon-

tinued treatment due to AEs, including 11 due to drug-related AEs per

investigator.

Conclusion: With longer f/u and additional patients, selpercatinib

demonstrates durable ecacy and intracranial activity regardless of line

of therapy. e safety prole of selpercatinib remains consistent with prior

reports.

Indication of source:

1 Previously presented at the IASLC-ESMO European Lung Cancer Conference

- 12th ELCC: March 2022, “FPN (Final Publication Number): 27P”, “Alexander

Drilon et al.” - Reused with permission

Disclosure Statement: e authors declare the following: Advisory boards and

lecture fees: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer-Ingelheim,

Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pzer, Roche,

Seattle Genetics, Takeda Research support (to institution); BMS, Janssen Pharma-

ceutica, Novartis, Pzer

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts150

256

Pacic-R Real-World Study: Treatment Duration and Interim

Analysis of Progression-Free Survival in Unresectable

Stage III NSCLC Patients Treated with Durvalumab After

Chemoradiotherapy

Daniel Christoph1; N. Girard2; H.J.M. Smit3; A. Sibille4; F. Mcdonald5;

F. Mornex6; M.C. Garassino7; A.R. Filippi8; S. Peters9; J.K. Field10;

V. Drageset Haakensen11; J. Bar12; C. Chouaid13; V. Bray14; S. Kao15;

W. Sawyer16; A. Allen17; M. Licour17; P. Garrido18; R. Fietkau19

1Department of Medical Oncology/Hematology, Evang. Kliniken Essen-Mitte,

Evang. Huyssens-Stiftung Essen Huttrop, Essen, Deutschland

2Institut du Thorax, Institut Curie & Montsouris, Paris, Frankreich

3Department of Pulmonary Diseases, Rijnstate Hospital, Arnheim, Niederlande

4Department of Pneumology and Allergology, Centre Hospitalier Universitaire

de Liège, Liegé, Belgien

5Lung Unit, The Royal Marsden NHS Foundation Trust, London, Vereinigtes

Königreich

6Department of Radiation Oncology, Centre Hospitalier Universitaire de Lyon,

Lyon, Frankreich

7Department of Hematology/Oncology, The University of Chicago, Chicago, USA

8Radiation Oncology Department, Fondazione IRCCS Policlinico San Matteo and

University of Pavia, Pavia, Italien

9Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV),

Lausanne, Schweiz

10Roy Castle Lung Cancer Research Programme, Department of Molecular

and Clinical Cancer Medicine, University of Liverpool, Liverpool, Vereinigtes

Königreich

11Department of Oncology, Oslo University Hospital, Oslo, Norwegen

12Institute of Oncology, Sheba Medical Centre, Ramat Gan, Israel

13Service de Pneumologie, CHI Créteil, Créteil, Frankreich

14Department of Medical Oncology, Liverpool Hospital, Liverpool, New South

Wales, Australien

15Department of Medical Oncology, Chris O’Brien Lifehouse, Camperdown,

NewSouth Wales, Australien

16Medical Aairs, Oncology, AstraZeneca, Gaithersburg, MD, USA

17Medical Aairs, Oncology, AstraZeneca, Paris, Frankreich

18Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spanien

19Department of Radiation Oncology, Universitätsklinikums Erlangen, Erlangen,

Deutschland

Background: Durvalumab (durva) consolidation therapy for up to 12

months(m) (PACIFIC regimen) is now standard of care in patients (pts)

with unresectable Stage III non-small-cell lung cancer (NSCLC) with-

out disease progression aer platinum-based (ptb) chemoradiotherapy

(CRT). PACIFIC-R assesses the eectiveness of durva in this pt popula-

tion in a real-life setting.

Methods: PACIFIC-R (NCT03798535) is a large international, observa-

tional study in pts who received ≥1 dose of durva (10 mg/kg Q2W) as part

of an AstraZeneca initiated expanded access program. Pts had completed

ptb-chemotherapy concurrent or sequential to radiotherapy within the

previous 12 weeks without evidence of disease progression.

Results: Outcomes were assessed in the full analysis set (N=1155).

Median time to durva initiation aer the end of RT was 52 days. Overall

median durva treatment duration was 337 days (11 m); 232 (20.1%) pts

received treatment for >12 m (50 [4.3%] for >14 m). Pts received a median

of 22 infusions. Reasons for/median time to treatment discontinuation

included completion of treatment (47.6%/11.8 m; investigator decision

per country protocol), disease progression (25.8%/5.1 m) and adverse

event (AE; 17.5%/2.8 m).

Pneumonitis was the most common AE leading to discontinuation (tem-

porary: 5.1%; permanent: 8.7%). 214 (18.5%) pts had any-grade pneumo-

nitis and/or interstitial lung disease (median time from durva start: 74

days [2.4 m]). Of these, most events were moderate (8.8%) in severity; 2

(0.2%) and 1 (0.1%) pts had a life-threatening or fatal event, respectively.

Interim analysis (51.8% of events) showed a median realworld(rw) PFS

(rwPFS) of 22.5 m (95% CI, 19.7-25.5). rwPFS by baseline PD-L1 status

and prior CRT will be included in the nal presentation.

Conclusions: ese results demonstrate the eectiveness of consolida-

tion durva aer CRT in a rw-cohort of pts with unresectable Stage III

NSCLC; pneumonitis events were mostly moderate in severity. Additional

data from an externally sponsored study with similar enrolment criteria in

Spain will be included in the nal presentation.

Disclosure Statement: e authors declare no conict of interest.

265

FINN (CA209-7MA): A non-interventional study (NIS) of rst-

line nivolumab plus ipilimumab combined with two cycles of

chemotherapy in metastatic non-small cell lung cancer

Sylvia Gütz1; Christian Schumann2; Harald Müller-Huesmann3; Daniela

Waldenberger4; Eckart Laack5

1St. Elisabeth-Krankenhaus Leipzig, Leipzig, Deutschland

2Klinikverbund Allgäu gGmbH, Kempten und Immenstadt, Deutschland

3Brüderkrankenhaus St. Josef, Paderborn, Deutschland

4Bristol-Myers Squibb, München, Deutschland

5Hämato-Onkologie Hamburg, Prof. Laack und Partner, Hamburg, Deutschland

Background: e immune checkpoint inhibitors nivolumab and ipilim-

umab have distinct but complementary mechanisms of action. Several

phase III and IV studies assessed the activity and safety of dual check-

point inhibitor blockade in the rst-line (1L) treatment of metastatic non-

small cell lung cancer (NSCLC). e randomized, open-label, phase III

CheckMate 9LA trial demonstrated a statistically signicant improvement

in overall survival, progression-free survival and overall response rate for

patients treated with nivolumab + ipilimumab combined with two cycles

of chemotherapy compared to chemotherapy alone. As the experience

with this combination therapy is mainly based on data from randomized

clinical trials, the NIS FINN was designed to collect real-life data during

the early post-market authorization approval period. e study aims to

describe patient characteristics and outcomes, safety prole, and treat-

ment patterns in normal clinical practice.

Methods: FINN (NCT04794010) is a national, prospective, observa-

tional, multicenter study. Overall, 825 patients diagnosed with metastatic

NSCLC, who start a systemic therapy with nivolumab + ipilimumab + 2

cycles of chemotherapy within the market authorization, will be enrolled.

e study collects data from approx. 80 oncology care facilities. Patients

will be followed for 5 years from Day 0 (ie, treatment initiation) until

death, withdrawal of consent, loss of follow-up, or end of the study.

During the follow-up period, assessments will be performed according

to routine local clinical practice. Data entry in the electronic case report

form (eCRF) will take place at Day 0, Week 6, Month 3, 6, 9, 12, 18, 24,

36, 48, and 60 (5 years aer nivolumab initiation). e primary objective

is overall survival. Secondary objectives include progression free survival,

treatment duration, patient characteristics, safety proles and patient-re-

ported outcomes (assessed by EQ-5D and NSCLC-Symptom Assessment

Questionnaire).

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 151

280

Checkpoint inhibitor monotherapy in potentially study-

eligible or non-study-eligible NSCLC patients in the German

CRISP Registry real-world cohort (AIO-TRK-0315)

Frank Griesinger1; Martin Sebastian2; Wolfgang Brückl3;

Horst-Dieter Hummel4; Bastian Jaeschke5; Jens Kern6; Class Wesseler7;

Martina Jänicke8; Annette Fleitz8; Stefan Zacharias8; Annette Hipper9;

Annika Groth9; Wilko Weichert10; Steen Dörfel11; Volker Petersen12;

Jan Schröder13; Jochen Wilke14; Wilfried Ernst Erich Eberhardt15;

Michael Thomas16

1Pius-Hospital Oldenburg, Hämatologie, Onkologie, Oldenburg, Deutschland

2Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie, Onkologie,

Frankfurt am Main, Deutschland

3Klinikum Nürnberg Nord, Nordklinikum, Innere Medizin III - Schwerpunkt,

Pneumologie, Nürnberg, Deutschland

4Universitätsklinikum Würzburg, Interdisziplinäres Studienzentrum, mit ECTU,

Würzburg, Deutschland

5Helios Dr. Horst Schmidt Kliniken Wiesbaden, IM III: Hämatologie, Onkologie,

Palliativmedizin, Wiesbaden, Deutschland

6Klinikum Würzburg Mitte , Standort Missioklinik Med. Klinik, mit Schwerpunkt

Pneumologie, Würzburg, Deutschland

7Asklepios Klinikum Harburg, Klinik für Pneumologie, Hamburg, Deutschland

8iOMEDICO AG, Freiburg im Breisgau, Deutschland

9AIO-Studien-gGmbH, Berlin, Deutschland

10Klinikum rechts der Isar der Technischen Universität München, Pathologie,

München, Deutschland

11Onkozentrum Dresden, Dresden, Deutschland

12Onkologische Schwerpunktpraxis, Dr. med. Volker Petersen, Heidenheim

a.d.B., Deutschland

13Gemeinschaftspraxis für Hämatologie und internistische Onkologie, Mülheim

a.d.R., Deutschland

14Schwerpunktpraxis Hämatologie & Internistische Onkologie, Fürth,

Deutschland

15Universitätsklinikum Essen, Westdeutsches Tumor Zentrum, Essen,

Deutschland

16Thoraxklinik-Heidelberg, Thoraxonkologie, Heidelberg, Deutschland

Background: Treatment for metastatic non-small cell lung cancer

(NSCLC) stratied according to biomarker testing results was shown in

RCTs to have benecial outcomes. Whether these improvements carry

over into real-world routine therapy is of great interest for patients (pts)

and physicians. Here we used the CRISP registry to compare pts charac-

teristics (chr) and outcomes of pts with PD-L1 TPS≥50% tumors treated

with checkpoint inhibitor monotherapy (CPI) who are deemed either

potentially study-eligible (se) or non-se (n-se).

Methods: CRISP (NCT02622581) is a prospective, observational, multi-

center, interdisciplinary clinical research platform that collects data on all

(sequential) treatments, patient and tumor chr, biomarker testing, clin-

ical and patient-reported outcomes in ~180 hospitals and practices in

Germany. Of currently 6300+ pts recruited, data from 473 pts with PD-L1

TPS≥50% recruited 12/2015 to 06/2019, receiving CPI as 1st-line treat-

ment was analyzed. Pts with following chr were deemed se: ECOG=0-1,

stage IV, no brain metastases, no HIV, no 2nd-tumor, or prior (neo)adju-

vant therapy.

Result: Of 473 pts analyzed, 191 were se in reection of inclusion criteria

for RCTs KEYNOTE 42 and 24, 282 pts were n-se representing the real-

world population. Although both groups are similar in age, CR/PR rates

(1%[se] vs. 2%[n-se] and 21% vs. 22%) and rates of stopped treatments

because of toxicity (10%, both), se pts had a longer PFS (10.0 months

(mts), 95% CI: 7.6-15.2 vs. 7.9 mts, 95% CI: 6.0-10.6) and OS (23.3 mts,

95% CI: 16.5-26.1 vs. 20.2 mts, 95% CI: 15.9-26.2) than n-se pts.

Conclusion: In recent years the use of CPI monotherapy in PD-L1

TPS≥50% pts increased in Germany, resulting in improved treatment

outcome. Potentially study-eligible pts prot more than potentially

non-study-eligible pts. e impact of CPI combination therapies or treat-

ment without CPI on both pts groups, will be subject of future analyses.

Indication of source: ESMO congress 2021

Disclosure Statement: e authors declare no conict of interest.

337

Niraparib (Nira) + Pembrolizumab (Pembro) Versus Placebo

(PBO) + Pembro rst line (1L) Maintenance Therapy in

Advanced Non-Small Cell Lung Cancer (NSCLC): ZEAL-1L Phase

3 Study

Martin Schuler1; Suresh S. Ramalingam2; Lei Shi3;

Melissa Whipple Neibauer3; Tara Frenkl3; Alexander Stojadinovic3;

Solange Peters4

1West German Cancer Center, University Hospital Essen, Essen, Deutschland

2Emory University, Winship Cancer Institute, Atlanta, USA

3GlaxoSmithKline, Oncology, Philadelphia, USA

4Lausanne University, Oncology Department, Lausanne, Schweiz

Background: Poly (ADP-ribose) polymerase (PARP) inhibitor, Nira,

exerts antitumor activity by blocking homologous recombination DNA

damage repair. Nira crosses the blood-brain barrier in animal models,

extending activity to the central nervous system (CNS). In preclinical

cancer models, Nira activates the STING pathway, recruits T cells, and

upregulates programmed death ligand-1 (PD-L1). Synergistic antitu-

mor eects of Nira+Pembro (PD-1 inhibitor) have been observed in

triple-negative breast cancer and Platinum (Pt)-resistant ovarian cancer

(TOPACIO/KEYNOTE-162), and as 1L therapy in advanced/metastatic

NSCLC (JASPER), with a tolerable safety prole.

Methods: ZEAL-1L is a Phase 3 randomized, double-blind, global

trial comparing ecacy and safety of 1L maintenance therapy with

Nira+Pembro vs PBO+Pembro in patients with conrmed Stage IIIB–IV

NSCLC. Patients with no known driver mutation, and no disease progres-

sion aer 4–6 cycles of 1L induction Pt-based chemotherapy+Pembro will

be screened. Approximately 650 patients will be recruited for randomiza-

tion (1:1) to Nira (200/300 mg orally, daily)+Pembro or PBO+Pembro. All

patients will continue Pembro (200 mg IV) up to 35 cycles from the start

of 1L induction therapy. Treatment will continue until disease progres-

sion, unacceptable toxicity, death, or loss to follow-up.

Result: e primary endpoints are progression-free survival assessed by

Blinded Independent Central Review (BICR) per Response Evaluation

Criteria in Solid Tumors v1.1 criteria and overall survival. Key secondary

endpoint is time to CNS progression by BICR. Patient-reported outcomes,

safety, and pharmacokinetic proles will also be evaluated.

Discussion: ZEAL-1L will provide evidence whether Nira can prolong

disease control aer 1L chemotherapy when combined with Pembro and

evaluate its potential to decrease risk of occurrence or progression of CNS

metastasis in advanced NSCLC.

Conclusion: is ongoing study is registered at clinicaltrials.gov

(NCT04475939). Recruitment began November 2020.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts152

368

Snier dogs can identify lung cancer patients from breath and

urine samples

Charlotte Feil1; Frank Staib1; Martin R. Berger2; Thorsten Stein1;

Irene Schmidtmann3; Andreas Forster4; Carl C. Schimanski1

1Klinikum Darmstadt GmbH, Medizinische Klinik II, Darmstadt, Deutschland

2Deutsches Krebsforschungszentrum , Arbeitsgruppe Toxikologie und

Chemotherapie, Heidelberg, Deutschland

3Johannes Gutenberg-Universität, Institut für Medizinische Biometrie,

Epidemiologie und Informatik, Mainz, Deutschland

4Lungenzentrum Darmstadt, Darmstadt, Deutschland

Background: Lung cancer is the most common oncological cause of death

in the Western world. Even if early diagnosis is critical for successful treat-

ment, no eective screening methods exist. In several studies, dogs were

trained to discriminate cancer samples from controls by sniing volatile

organic compounds (VOC) as diagnostic biomarkers. In this study we

evaluated the abilities of a specically trained dog to distinguish samples

from lung cancer patients from matched healthy controls.

Methods: is single center, randomized, double-blind clinical trial with

432 patients was approved by the local ethics committee (FF20/2016).

Aer being conditioned with breath and urine samples of 150 controls

and 36 cancer patients comprising all stages, further 205 controls and 41

cancer patients were included for study phase. Two breath and urine sam-

ples were collected from each patient, and shock frozen. Only samples

from new subjects were presented to the dog.

Result: Using a combination of urine and breath samples, the dog cor-

rectly predicted 40 out of 41 cancer samples, leading to an overall detec-

tion rate of 97.6% (95% CI [87.1 %, 99.9 %]). Using urine samples only the

dog achieved a detection rate of 87.8% (95% CI [73.8 %, 95.9 %]). With

breath samples, the dog correctly identied cancer in 32 of 41 samples,

resulting in a detection rate of 78% (95% CI [62.4 %, 89.4 %]).

Discussion: Breath samples alone might be inferior for olfactory detec-

tion than urine samples. e combined method of both samples showed a

promising result as a non-invasive, riskless method. With dogs being indi-

viduals and therefore their use hard to standardize, further target com-

pounds and bias to olfactory detection need to be identied to develop an

electronic nose as a bionic approach.

Conclusion: Olfactory detection of lung cancer by specically trained

dogs is highly suggestive to be a simple and non-invasive tool to detect

lung cancer using VOC pointing to cancer growth in breath and urine

samples.

Disclosure Statement: e authors declare no conict of interest.

Published in BMC Cancer: https://doi.org/10.1186/s12885-021-08651-5

369

5th Nationwide Tumor-biological Testing Survey in Patients

with NSCLC in Germany – Current Results and Development

ofTesting Behavior since 2012

Helmut Ostermann1; Sonja Loges2

1LMU Klinikum, München, Deutschland

2Universitätsklinikum Mannheim, Department of Personalized Oncology,

Division of Personalized Medical Oncology (A420), DKFZ, , Mannheim,

Deutschland

Background: Targeted drug therapy following assessment of molecu-

lar alterations in tumor tissue has become standard-of-care in stage IV

NSCLC and recently as adjuvant treatment following resection in stage

IB-IIIA as well. Guidelines recommend the use of companion diagnostic

guided drug therapy from which many patients benet considerably. We

want to determine whether testing in Germany is performed as per guide-

line recommendations.

Methods: Experienced oncologists from dierent types of health care

institutions (certied lung cancer centers, university/ non-university

hospitals, oce-based physicians partly associated with network associ-

ations (nNGM, ZPM)) are asked to answer a questionnaire on the details

of testing. Data are analyzed by explorative analysis. e current results

are broken down by institution and compared with those from previous

surveys to analyze the development of testing behavior. In addition, this

year testing behavior in early stage NSCLC is evaluated.

Result: As previous surveys have shown, biomarker testing in Germany

has generally improved, however testing rates are biomarker dependent

and seem to reach partially a plateau at ~ 80% as indicated by 2019 rates

from EGFR 80%, PD-L1 81%, ALK 77%. In 2019 the greatest potential

for improvement was within the lung centers, where 18% of the patients

did not receive any type of biomarker analysis. Overall there is still poten-

tial for improvement in Germany in terms of the optimal use of therapy

options. ese data will again be examined in the new survey which is

currently ongoing. We will present the results and discuss the develop-

ment of testing in Germany from 2012 to 2021.

Conclusion: Despite guideline recommendations it appears that there is

still a signicant number of patients in whom tumor-biological testing is

not done and, therefore, access to optimal treatment may not be possible.

e results that will be presented will clarify whether important improve-

ments in the rate of testing have occurred within the last 2 years and put

that in a 10 year perspective.

Disclosure Statement: e authors declare the following: is study was support-

ed by Astra Zeneca

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 153

370

Tepotinib in patients (pts) with MET exon 14 (METex14)

skipping non-small cell lung cancer (NSCLC): Interim analysis

of VISION Cohorts A and C

Frank Griesinger1; Michael Thomas2; Niels Reinmuth3; Martin Wermke4;

Tobias Overbeck5; Jürgen Alt6; Sven Henschke7; Thomas Wehler8;

Sebastian Ochsenreither9; Marina Chiara Garassino10; Enriqueta Felip11;

Hiroshi Sakai12; Rolf Bruns13; Gordon Otto14; Andreas Johne14;

Paul K. Paik15,16

1Pius-Hospital, University Medicine Oldenburg, Department of Hematology

and Oncology, University Department Internal Medicine-Oncology, Oldenburg,

Deutschland

2Thoraxklinik, University Heidelberg and Translational Lung Research Center

Heidelberg (TLRC-H), The German Center for Lung Research (DZL), Heidelberg,

Deutschland

3Asklepios Lung Clinic, Munich-Gauting, Deutschland

4Technical University Dresden, NCT/UCC Early Clinical Trial Unit, Dresden,

Deutschland

5Clinic for Hematology and Medical Oncology, University Medical Center

Göttingen, Göttingen, Deutschland

6University Medical Center of the Johannes Gutenberg-University Mainz, Mainz,

Deutschland

7Saarland University Hospital, Homburg, Deutschland

8Evangelisches Krankenhaus Hamm GmbH, Hamm, Deutschland

9Charité Comprehensive Cancer Center, Berlin, Deutschland

10Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei

Tumori, Milan, Deutschland

11Department of Oncology, Vall d’Hebron Institute of Oncology (VHIO),

Barcelona, Spanien

12Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan

13Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Deutschland

14Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Deutschland

15Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New

York, USA

16Weill Cornell Medical College, New York, USA

Background: We report outcomes for tepotinib – a highly selective,

potent MET inhibitor – in patients (pts) with METex14 skipping in

VISION Cohorts A (primary analysis) and C (conrmatory), by prior

therapies. ese are relevant for clinical practice, given the approval by the

European Commission for tepotinib in pts with advanced NSCLC harbor-

ing METex14 skipping, previously treated with immunotherapy (IO) and/

or platinum-based chemotherapy (CT).

Methods: Pts with advanced/metastatic METex14 skipping NSCLC

received 500 mg (450 mg active moiety) tepotinib once daily. Safety

was assessed in all pts who received tepotinib, and ecacy in pts with

≥3 months’ follow-up (data cut-o: Feb 1, 2021). Primary endpoint was

objective response by IRC (RECIST 1.1).

Result: Of 275 pts evaluable for ecacy, 138 were previously treated

(2L+): median age 70.9 years (range, 41–89), 51% female, 40% smok-

ing history, and 42.0% enrolled in Europe. 86% of 2L+ pts had prior

platinum-based CT, 53% had prior IO (37% as monotherapy, 15% had

IO-CT). Objective response rate (ORR) was 44.2% (95% CI: 35.8, 52.9),

with median (m) DOR of 11.1 months (8.4, 18.5). Disease control rate

was 75.4% (67.3, 82.3), mPFS was 11.0 months (8.2, 12.4), and mOS was

19.9 months (15.8, 22.3). Ecacy was observed regardless of types of prior

therapies, including CT and/or IO. 137 pts were treatment-naïve (1L):

median age 74.6 years (range, 47–94), 50% female, 53% smoking history,

and 60.6% enrolled in Europe. ORR was 54.0% (45.3, 62.6) and mOS was

17.6 months (13.4, 29.7). Overall, pts with brain metastases at baseline

(51/275 [18.5%]) had systemic ORR of 52.9% (38.5, 67.1), and mDOR

of 9.0 months (5.6, ne). Treatment-related adverse events (TRAEs) were

mostly mild-moderate across therapy lines; Grade ≥3 TRAEs occurred in

33.1% of 1L pts and 25.9% 2L+ pts.

Conclusion: In VISION – the largest clinical trial of a MET inhibitor

in pts with METex14 skipping NSCLC – tepotinib demonstrated robust

and durable clinical activity in both 2L+ and 1L pts, and in pts with brain

metastases, with a tolerable safety prole.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

413

Survival outcomes in patients with sarcomatoid pleural

mesothelioma: a retrospective analysis from the last two

decades

Helge G. Bischo1; Rajiv Shah1; Miriam Blasi1; Jonas Kuon1; Petros

Christopolous1; Inn Chung1; Albrecht Stenzinger2; Mark Kriegsmann2;

Julia Glade2; Laura V. Klotz3; Martin E. Eichhorn3; Sabine Wessels1;

Thomas Muley4; Felix J.F. Herth5; Michael Thomas1

1Thoraxklinik, Thoraxonkologie, Heidelberg,

2Pathologisches Institut, Universität Heidelberg

3Thoraxklinik, Thoraxchirurgie

4Thoraxklinik, Translationale Forschung

5Thoraxklinik, Pneumologie und Beatmungsmedizin

Background: Sarcomatoid pleural mesothelioma (SM) is a rare histo-

logical sub-type of mesothelioma associated with poor overall survival

(OS). e therapeutical approach is based on systemic chemotherapy

(CT), despite a lower chemosensitivity as compared with the epithelioid

counterpart.

Methods: In this single-center, retrospective study we evaluated clinico-

pathological features, frontline treatment and survival outcomes of 63

patients with an ascertained pathological diagnosis of SM treated in our

center from 2000 until 2020.

Result: e median age was 71 years (range 45-88), 57 (90%) patients

were male. At the time of diagnosis, 52 (83%) patients had an Eastern

Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1.

Twenty (32%) patients received best supportive care (BSC), 39 (62%)

received rst-line chemotherapy (CT), 3 (5%) trimodality treatment and

1 (2%) patient underwent surgery only. In the subgroup of patients with

rst-line CT, 26 (67%) were treated with a platinum-based doublet-CT,

while 13 (33%) received single agent CT (mono-CT).

Patients treated with CT had a median progression-free survival (PFS) of

2 months (95% condence interval (CI) 1.24-2.76) and a median OS of

7 months (95% CI 5.26-8.74). Compared with patients with mono-CT,

patients receiving doublet-CT had a longer median OS (3 months vs. 8

months, HR 0.42 [95% CI, 0.21-0.85], p=0.009). e median PFS was 3

months for patients receiving doublet-CT and 1 month for patients treated

with mono-CT (HR 0.87 [95% CI 0.43-1.74], p=0.63) e median OS of

patients receiving BSC was 2 months (95% CI 0.95-3.05). No signicant

dierence in OS was found when comparing mono-CT with BSC (3 vs. 2

months, HR 0.55 [95% CI, 0.26-1.17], p=0.082) and this was consistent in

the subgroup of patients aged ≥ 70 years (OS 3 vs. 2 months, HR 0.73 [95%

CI 0.3-1.75], p=0.440).

Conclusion: In patients with SM not eligible for frontline platinum-based

doublet-CT, treatment with single agent CT should be carefully evaluated,

since the survival benet is unclear.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts154

433

Clinical and pathological features and prognosis of non-small

cell lung cancer (NSCLC) patients with adenocarcinomas

without TTF1 and Napsin A expression

Franziska Kraus1; Georg Nilius2; Servet Bölükbas3; Imke Stöver4;

Andreas Koziorowski4; Florian Grabellus5

1Kliniken Essen-Mitte, Onkologie, Essen, Deutschland

2Kliniken Essen-Mitte, Pneumologie, Essen, Deutschland

3Klinken Essen-Mitte, Thoraxchirurgie, Essen, Deutschland

4Gemeinschaftspraxis für Strahlentherapie, Essen, Deutschland

5Zentrum für Pathologie Essen-Mitte, Essen, Deutschland

Background: TTF-1 helps to conrm a primary lung origin in 75-85%

of lung adenocarcinoma. But in the remaining patients (pts) TTF-1 is

not expressed. Clinical, pathological and molecular features about last

mentioned subgroup is lacking. Enteric dierentiation can occur in lung

adenocarcinoma and when this component exceeds 50%, the tumor is

classied as pulmonary adenocarcinoma with enteric dierentiation

(PAED).

Methods: Lung adenocarcinoma pts who were diagnosed from 01/2018

until 04/2021 were identied by review of the pts records. Only pts whose

tumors didn`t express TTF-1 and Napsin A were evaluated. Enteric ade-

nocarcinomas were conrmed by expression of CDX2, CK20 or MUC2.

Primary tumors of the gastrointestinal tract were excluded by PET-CT/

CT/endoscopy.

Result: A total of 53 pts (31 males (58.5%), 22 females (41.5%)) were

found. Median age was 68 ys (range: 54-83 ys). 24 pts were diagnosed

at a local stage, 29 pts had metastatic disease (stage IV). Tumors with

any PD-L1 expression were found in about 50 % of the pts. Median dis-

ease-free survival of 17 pts with surgical resection was 8 mths, median

progression-free survival of any stage IV pts (29) with rstline systemic

treatment was 3 mths. No dierence between chemotherapy and chemo-/

immunotherapy treatments were noticed (median PFS: 3 mths (range:

0-12) vs. 3 mths (range: 0-15). Furthermore, 15 pts suered from PAED.

Regarding molecular alterations in stage IV pts, a higher percentage of

KRAS mutations was found in PAED pts (37 % vs. 24.5 %).

Discussion: Compared to available data from TTF-1 positive patients

receiving rstline systemic treatment, the prognosis of TTF-1-negative

pts seems to be far poorer.

Conclusion: At present, this is the largest series of clinical and patho-

logical features of lung adenocarcinoma pts without TTF1- and Napsin

A-expression and particularly with enteric dierentiation.

Disclosure Statement: e authors declare no conict of interest.

462

Comparison of lung cancer-centersand non-centers: Regional

dierences in the patients characteristics and therapy of

bronchial carcinoma?

Johanna Oswald1; Tobias Robold1; Michael Gerken2,3; Luisa Horn1;

Konstantin Fitilidis1; Monika Klinkhammer-Schalke2,3;

Hans-Stefan Hofmann1

1University Hospital Regensburg, Department of Thoracic Surgery, Regensburg,

Deutschland

2Institute for Quality Management and Health Services Research, University of

Regensburg, Tumour Centre, Regensburg, Deutschland

3Bavarian Health and Food Safety Authority, Bavarian Cancer Registry, Regional

Centre Regensburg, Deutschland

Background: e “Further development of oncological care structures

and quality assurance” is part of the National Cancer Plan of the Federal

Ministry of Health. e present work is intended to contribute to a trans-

parent presentation of current care by means of a regional comparison of

patient and treatment structures.

Methods: In a retrospective study based on data from a population-based,

clinical cancer registry from the Lower Bavaria/Upper Palatinate region,

the aim is to investigate whether local, oncological structure requirements

show an inuence on therapy and patient outcome. For this purpose,

patient data from the years 2015-2018 from lung cancer centres (group1,

corresponding to the structural specications of the German Cancer

Society) were compared with data from clinics not certied as lung cancer

centres (group 2).

Result: Data were collected from 3952 patients; aer exclusion, 3686

remained for the analyses. e distribution of the analysed patients

in the two comparison groups is 55% in group 1 and 45% in group 2.

Unadjusted, there is a signicant survival advantage for patients in lung

centres compared to non-certied hospitals, which also remains in the

multivariable model. If the stage distribution is taken into account, a sig-

nicant survival time advantage is shown in stages I and II for group 1.

For stages III and IV, no signicant dierence in survival compared to the

comparison group can be observed.

Discussion: e limitations of a retrospective cohort-study were ade-

quately addressed with risk-adjustment by multivariable regression

analyses.

Conclusion: e data already available show an advantage in overall sur-

vival for treatment in lung cancer centres, but at the same time also a less

favourable distribution of risk factors in the comparison group. e rea-

sons for the signicant dierences must be worked out in further analyses,

considering additional factors.

Disclosure Statement: e authors declare no conict of interest.

482

The peripheral T-cell receptor repertoire in metastatic non-

small-cell lung cancer patients receiving rst- or second-line

immunotherapy and the inuence of CMV seropositivity

Mariam Elshiaty1,2; Fabienne Lusky1,2; Farastuk Bozorgmehr1,2;

Isabel Poschke3; Hannah Schindler1,2; Arlou K. Angeles2,4; Jonas Kuon1;

Rajiv Shah1; Simon J. Ogrodnik2,4; Lena Gaissmaier1,2; Marc A. Schneider2,5;

Daniel Kazdal2,6; Michael Allgäuer6; Michael Meister2,5; Thomas Muley2,5;

Felix J. Herth2,7; Hauke Winter2,8; Florian Eichhorn2,5,8; Paul Schnitzler9;

Albrecht Stenzinger2,6; Holger Sültmann2,4; Michael Thomas1,2;

Petros Christopoulos1,2

1Thoraxklinik at Heidelberg University Hospital and National Center for Tumor

Diseases, Department of Thoracic Oncology, Heidelberg, Deutschland

2Translational Lung Research Center Heidelberg (TLRC), German Center for Lung

Research (DZL), Heidelberg, Deutschland

3Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Division of Molecular

Oncology of Gastrointestinal Tumors, Heidelberg, Deutschland

4Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Division of Cancer

Genome Research, Heidelberg, Deutschland

5Thoraxklinik at Heidelberg University Hospital, Translational Research Unit,

Heidelberg, Deutschland

6Institute of Pathology Heidelberg University, Heidelberg, Deutschland

7Thoraxklinik at Heidelberg University Hospital and National Center for Tumor

Diseases, Department of Pneumology and Critical Care Medicine, Heidelberg,

Deutschland

8Thoraxklinik at Heidelberg University Hospital and National Center forTumor

Diseases, Department of Thoracic Surgery, Heidelberg, Deutschland

9Center for Infectious Diseases, University Hospital of Heidelberg, Department

of Virology

Background: Metastatic non-small-cell lung cancer (NSCLC) patients

oen receive immunotherapy (IO) as rst- (1L) or second-line (2L) treat-

ment, but the majority do not respond, and reliable biomarkers for IO

benet are lacking.

Methods: We retrospectively analyzed baseline blood samples of

IO-treated stage IV NSCLC patients, who either experienced rapid pro-

gression (RP, progression-free survival [PFS] < 6 months), long-term ben-

et (LR, [PFS] >12 months), or an intermediate course (IR, [PFS] 6-12

months). e patients were divided in 3 cohorts: patients receiving IO as

1L treatment (1L-IO, n=45), patients receiving IO as 2L treatment (2L-

IO, n=36) and patients receiving IO combined with chemotherapy as 1L

treatment (1L-CTxIO, n=38). Age-matched healthy donors (n=20) were

included as controls. e T cell receptor (TCR) repertoire was analyzed

by TCRβ next-generation sequencing using the immunoSEQ platform

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 155

(Adaptive Biotechnologies). Furthermore, available serum samples

(n=86) were tested for CMV seropositivity.

Result: No signicant dierences in the TCRβ clonality of baseline blood

samples were noted between the LR and RP subsets of each cohort (1L-

IO, 2L-IO, 1L-CTxIO). 2L-IO patients showed a higher clonality than

both the control and 1L-IO cohorts (0.086 vs 0.048 and vs 0.046, p <0.05).

Based on available serum samples, CMV seropositivity was 62% (53/86)

and correlated positively with clonality (r=0.661, p <0.001), which was

signicantly higher in CMV positive samples (0.099 vs 0.026, p <0.001).

Discussion: In NSCLC, the TCRβ repertoire clonality in peripheral blood

increases with previous treatments, but baseline values are not predictive

of response to IO or CTxIO. CMV seropositivity is common (>50%) in

NSCLC and appears to inuence TCRβ clonality more than previous

treatments.

Conclusion: Baseline TCRβ repertoire clonality alone is not a predictive

biomarker for immunotherapy outcome in NSCLC. Ongoing work is eval-

uating the association with tumor characteristics, as well as longitudinal

changes and their potential relationship with the clinical course.

Disclosure Statement: e authors declare the following: P.C. declares research

funding from AstraZeneca, Novartis, Roche, Takeda, and advisory board/lecture/

educational fees from AstraZeneca, Boehringer Ingelheim, Chugai, Kite, Novartis,

Pzer, Roche, and Takeda. M.E. declares no conict of interest.

500

Upfront and repeated stereotactic radiosurgery in patients

with brain metastases from NSCLC – Clinical outcome and

validation of prognostic scores

Anna Krämer1; Sebastian Adeberg1; Dorothea Kronsteiner2; Laila König1;

Fabian Schunn1; Farastuk Bozorgmehr3; Petros Christopoulos3;

Tanja Eichkorn1; Stefan Rieken4; Jürgen Peter Debus1; Rami El Shae1,4

1RadioOnkologie und Strahlentherapie, Universitätsklinikum Heidelberg,

Heidelberg, Deutschland

2Institut für Medizinische Biometrie und Informatik, Universitätsklinikum

Heidelberg, Heidelberg, Deutschland

3Innere Medizin, Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland

4Klinik und Poliklinik für Strahlentherapie und Radioonkologie ,

Universitätsmedizin Göttingen , Göttingen, Deutschland

Background: Approximately 40% of NSCLC patients develop brain

metastases (BM) during the course of their disease. Stereotactic radiosur-

gery (SRS) instead of whole-brain radiotherapy (WBRT) is increasingly

administered as an upfront treatment to patients with one or multiple

BM. We present outcomes and validation of prognostic scores for a large

cohort of patients with BM from NSCLC treated with upfront SRS.

Methods: We retrospectively analyzed 199 patients with a total of 268

SRS courses for 539 brain metastases. Median patient age was 63 years

(IQR: 56-69) and the median initial number of metastases per patient was

2 (IQR: 1-4, Range: 1-17). 54 (27,2%) patients received more than one SRS

course. SRS was delivered at a dose of 20 Gy. For larger BM, dose reduc-

tion to 18 Gy or hypofractionated SRS in 6 fractions was applied. In cases

of intracranial progression, repeated SRS was delivered when clinically

feasible. We analyzed the BMV-, the RPA-, the GPA- and the lung-mol

GPA score. Cox proportional hazards models with univariate and multi-

variate analyses were tted for overall survival (OS) and intracranial pro-

gression-free survival (icPFS).

Result: 64 patients died, seven of them of neurological causes. 38 patients

(19,3%) required a salvage WBRT due to intracranial progression. Median

OS was 38,8 months (IQR: 6-NA). In univariate analysis as well as mul-

tivariate analysis, the Karnofsky performance scale index (KPI) ≥ 90%

(p=0,012 and p=0,041) remained as independent prognostic factor for

longer OS. All four prognostic scoring indices could be validated for OS

assessment (BMV p=0,007; RPA p=0,026; GPA p=0,003; lung-mol GPA

p=0,05).

Discussion/Conclusion: In this large cohort of NSCLC patients with

BM treated with upfront and repeated SRS, OS was markedly favourable,

in comparison to literature. Only few patients required salvage WBRT

or died of neurological causes. Upfront SRS is an eective treatment

approach in those patients and can decidedly reduce the impact of BM on

overall prognosis. Furthermore, the analysed scores are useful prognostic

tools for OS prediction.

Disclosure Statement: e authors declare no conict of interest.

Lung Cancer

510

A multi-methods preclinical platform to inform clinical

decision making in lung cancer patients with uncommon

driver mutations - A project from the national Network

Genomic Medicine.

Melanie Janning1,2,3,4, Martin Ziegler1,2,4, Corinna Albers-Leischner3,

LorenaSalgueiro1,2,4, Christina Alidousty5, Felix C Saalfeld6,

SebastianMerker7, Carina Wenzel8, Daniel Stange7,9, Jürgen Wolf10,

Reinhard Büttner5, Christian Brandts11, Martin Wermke6, Sonja Loges1,2,3,4

1Division of Personalized Medical Oncology (A420), Deutsches

Krebsforschungszentrum, Heidelberg, Deutschland

2Department of Personalized Oncology , University Hospital Mannheim,

Medical Faculty Mannheim, University of Heidelberg, Mannheim, Deutschland

3Department of Oncology, Hematology and Bone Marrow Transplantation with

section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg,

Deutschland

4DKFZ-Hector Institute at the University Hospital Mannheim, Mannheim,

Deutschland

5Institute of Pathology, University Hospital Cologne, Cologne, Deutschland

6Clinic for Internal Medicine I, Medical Faculty and University Hospital Carl

Gustav Carus, Technische Universität Dresden, Dresden, Deutschland

7National Center for Tumor Diseases (NCT) Dresden, German Cancer Research

Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University

Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany;

Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany

8Institute of Pathology, Medical Faculty and University Hospital Carl Gustav

Carus Dresden

9Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and

University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden,

Deutschland

10Department of Internal Medicine, Center for Integrated Oncology, University

Hospital Cologne, Cologne, Deutschland

11Department of Medicine, Hematology/Oncology, University Hospital

Frankfurt, Goethe University, Frankfurt, Deutschland

Background: Increased use of next generations sequencing revealed a

substantial number of patients with uncommon variants of mutations.

For lung cancer patients we estimated, that ~ 2000 patients are newly

diagnosed per year with such uncommon variants in Germany. Little is

known about possible driver function and therapeutic susceptibilities of

individual mutations or their combinations. Because patients with driver

mutations benet more from targeted therapies than chemotherapies,

there is an unmet clinical need to determine the clinical implications of

carrying such variants. Here we present a novel multicenter platform of

the national Network Genomic Medicine Lung Cancer (nNGM) with the

aim to generate preclinical real-time evidence on uncommon mutations

to support clinical decision making.

Methods: In-silico prediction modelling together with cell-based assays

such as the IL3-dependent Ba/F3 system will be used for prediction of

driver function. Inhibitory potency for dierent drugs will be determined

using protein-ligand binding and viability assays. Patient-derived cancer

organoids (PDO) are continuously established to perform drug screens

and long term exposure of cultures will be analyzed towards resistance

development.

Result: e platform will be available for all nNGM participating cen-

ters. Aer notication of the mutation by the treating physician, possi-

ble driver activity and sensitivity analyses based on in-silico and in-vitro

assays will be available within 4 weeks. is information will be fed into

the nNGM digital annotation platform MURIPEDIA and be available to

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts156

inform nNGM MTBs. Correlation of clinical response with predicted sen-

sitivity proles will inform a self-learning, evidence-generating system. A

biobank of PDO is being generated and a drug plate of selected TKIs is

being constructed.

Discussion: We will evaluate to what extend pre-clinical data can be used

to inform clinical decision making

Conclusion: e platform in combination with collection of clinical fol-

low-up will generate evidence for treatment of uncommon mutations.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

518

Proteasomal processing alterations as a novel mechanism of

immune escape in NSCLC straties patients for response to

immune checkpoint blockade

Michael Wessolly1; Marcel Wiesweg2; Sabrina Borchert1; Hendrik Beckert3;

Susann Stephan-Falkenau4; Elena Mairinger1; Jens Kollmeier5;

Clemens Aigner6; Christian Taube3; Jeremias Wohlschlaeger7;

Thorsten Bauer5; Thomas Mairinger4; Kurt Werner Schmid1;

Martin Schuler2; Henning Reis1; Fabian Dominik Mairinger1

1Institute of Pathology, University Hospital Essen, Deutschland

2Clinical for internal medicine (tumor research), West German Cancer Center,

University Hospital Essen, Deutschland

3Department of Pulmonary Medicine, University Hospital Essen, Deutschland

4Department of Tissue Diagnostics, Helios Klinikum Emil von Behring,

Deutschland

5Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Deutschland

6Department for Thoracic Surgery, University Hospital Essen, Deutschland

7Department of Pathology, Diakonissenkrankenhaus Flensburg, Deutschland

Background: Immunotherapy has recently become a game changer in

the treatment of treatment-naive and oncogenic-driver wild type NSCLC,

with immune checkpoint inhibitors (ICIs) frequently used. Although ICIs

are an eective therapy, the main problem of primary resistance remains.

Not much attention, however, has been paid to immunogenic quality of

tumor neoantigens. In previous work, we identied altered epitope pro-

cessing as an important mechanism for tumor immune escape.

Methods: FFPE samples from patients with treatment-naïve advanced

NSCLC that received 1L anti-PD-1 ICI therapy were analyzed for both

WES and digital gene expression analysis (NanoString nCounter analy-

sis). For prediction of proteasomal cleavage, the machine learning tool

NetChop 3.1 was used. Results were introduced to an explorative data

analysis for clinicopathological and follow-up data, resulting in a compar-

ative patient stratication for ICI treatment.

Results: Patients showing processing escapes revealed a signicantly

shortened OS aer ICI treatment (p=0.008, HR: 2.85, 95% CI: 1.27-6.41).

e one-year OS rate diers from 26.4% to 63.1% (95% CI: 13.8-50.5 vs.

45.5-87.5). Moreover, a signicantly shortened time-to-treatment-failure

(TTF) time has been revealed (p=0.002, HR: 2.78, 95% CI: 1.41-5.46).

e one-year TTF rate diers from 15.7% to 60.2% (95% CI: 7.1-34.7 vs.

42.8-84.7).

Discussion: In line with our previous ndings from real-world data based

on targeted amplicon-based sequencing, we can validate the eect of a

processing escape phenotype on patient survival and outcomes aer ICI.

e determination of processing escapes in the subset of expressed genes

revealed a clear trend for both shortened TTF and OS aer ICB in the

processing escape group.

Conclusion: We have demonstrated the negative impact of mutations

leading to non-immunogenic neoantigens on patient’s response to ICI

therapy. is should be considered for further adaptions of diagnostic

processes to overcome therapy resistance.

Disclosure Statement: e authors declare no conict of interest.

551

CRP kinetics as an early predictive biomarker for response to

anti-PD-L1 therapy in advanced NSCLC

Jonas Saal1; Niklas Klümper2; Fiamma Berner3; Christa Lichtensteiger3;

Annkristin Heine1; Franz-Georg Bauernfeind1; Jörg Ellinger2;

Peter Brossart1; Manuel Ritter2; Michael Hölzel2; Lukas Flatz3; Tobias Bald4

1Medizinische Klinik 3 für Hämatologie und Onkologie, Universitätsklinikum

Bonn, Bonn, Deutschland

2Klinik für Urologie, Universitätsklinikum Bonn, Bonn, Deutschland

3Klinik für Dermatologie, Universitätsklinikum Tübingen, Tübingen ,

Deutschland

4Institut für experimentelle Onkologie, Universitätsklinikum Bonn, Bonn,

Deutschland

Background: Predictive biomarkers for response to immune-check-

point blockade (ICB) are lacking. Recently C-reactive protein (CRP) are

kinetics were associated with response to ICB in patients suering from

renal cell carcinoma (1). Here we investigated, if CRP are kinetics can

predict response and outcome in ICB-treated non-small-cell lung cancer

(NSCLC) patients.

Methods: A prospective cohort of 107 patients with advanced stage

NSCLC treated with ICB alone (79%) or in combination with chemother-

apy (21%) was analyzed for CRP kinetics and outcome. e results were

veried in a retrospective cohort including 105 patients. Patients were

classied by CRP kinetics as are-responders (increase in CRP levels to at

least 2x baseline with subsequent drop below baseline within 3 months),

responders (CRP decreasing at least 30% below baseline within 3 months)

and non-responders (others).

Results: CRP are correlated with improved OS when compared to

responders and non-responders (34.0 vs 17.9 vs 6.6 months, HR 0.26) and

PFS (16.8 vs 7.9 vs 2.3 months, HR when compared to non-responders

0.32). Overall response rate (ORR) in rst staging was 95.7% in are-re-

sponders, 66.7 % in responders and 40.0% in non-responders. We could

verify those results in a retrospective cohort (HR when compared to

non-responders for OS 0.49 and for PFS 0.44).

Discussion: Our data provide the rst evidences that early CRP kinet-

ics correlate with response and survival in ICB-treated NSCLC patients.

Hence CRP values are widely available, easy to obtain and can be evalu-

ated as early as 4-6 weeks aer start of therapy CRP-kinetics could provide

a valuable on-treatment biomarker for response in NSCLC patients.

Conclusion: CRP are kinetics can predict response and survival in ICB

treated NSCLC.

Indication of source:

1. Fukuda et al. Impact of C-reactive protein are-response on oncological

outcomes in patients with metastatic renal cell carcinoma treated with

nivolumab. J Immunother Cancer. 2021;9(2).

Disclosure Statement: e authors declare no conict of interest

606

Safety and ecacy of simultaneously performed radiotherapy

in patients with small-cell lung cancer undergoing

atezolizumab treatment

Julia Galuba1; Imke Stöver2; Andreas Koziorowski2; Servet Bölükbas3;

Georg Nilius4; Daniel Christoph1,1

1Department of Medical Oncology, Evang. Kliniken Essen-Mitte, Essen,

Deutschland

2Practice for Radio-Oncology Essen, Essen, Deutschland

3Department of Thoracic Surgery, Evang. Kliniken Essen-Mitte, Essen,

Deutschland

4Department of Pneumology, Evang. Kliniken Essen-Mitte, University Witten-

Herdecke, Essen, Deutschland

Background: In 2019 atezolizumab was approved for extended disease

small cell lung cancer (SCLC) in combination with cytotoxic chemother-

apy. In the clinical trial IMpower133 only 22 out of 201 patients (pts)

received prophylactic cranial radiotherapy (PCI) during their treatment

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 157

with atezolizumab. To our knowledge, no other clinical studies have

reported ecacy or safety regarding the combination of radiotherapy

(PCI, whole brain radiotherapy or consolidating thoracic radiother-

apy (CTR)) with atezolizumab as single agent or in combination with

chemotherapy.

Methods: We performed a retrospective data analysis of all pts with SCLC

who were treated at the Department of Medical Oncology, Evang. Kliniken

Essen-Mitte from January 2019 until December 2021. Pts with combined

chemo-/immunotherapy as induction treatment or with immunotherapy

as maintenance were compared to those without any immunotherapy

receiving similar radiotherapies, including pulmonary function (if possi-

ble), Odds-Ratio for adverse events, progression-free-survival (PFS) and

overall-survival.

Result: 48 SCLC pts underwent cranial and/or thoracal irradiation.

Atezolizumab was administered to 21 of them. A total of 24 pts received

combined chemo-/immunotherapy without any radiotherapy. ere were

no severe AEs in pts with cranial radiotherapy regardless of simultaneous

administration of atezolizumab. In pts with CTR, there was no signicant

dierence in grade I to III AEs. A statistical trend towards an improved

median PFS was found in patients with CTR. ere is preliminary evi-

dence for no deterioration of pulmonary function for pts receiving

simultaneous CTR and atezolizumab compared to pts with CTR without

atezolizumab.

Discussion: Although it was only a small retrospective study, there is no

evidence for additional toxicity for patients undergoing simultaneous

immunotherapy and radiotherapy. Further prospective studies are needed.

Conclusion: e addition of simultaneous radiotherapy to immunother-

apy seems not to be associated with increased toxicity in SCLC patients.

Disclosure Statement: e authors declare the following: Daniel C. Christoph

reports personal fees, non-nancial support and other from AstraZeneca, Bayer,

Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai, MSD Sharp & Dohme,

Novartis, Pzer, Roche, and Takeda.

694

Curative treatment in EGFR mt+ NSCLC stage III by induction

TKI-chemotherapy combination: Feasibility and outcome

in 10 cases

Frank Griesinger1; Julia Roeper1; Kay Willborn2; Regina Prenzel2;

Douglas Scriba2; Martin Sebastian3

1Universitätsklinik Innere Medizin-Onkologie Universität Oldenburg, Pius

Hospital Oldenburg, Oldenburg, Deutschland

2Pius Hospital Oldenburg, Oldenburg

3Universitätsklinikum Frankfurt, Frankfurt

Background: EGFR TKI’s are a mainstay in the treatment of metastatic

NSCLC with EGFR mt+, however their use in the curative setting is not

yet standard of care. Recently, combination of TKI and chemotherapy

has been shown to improve ORR, PFS and OS in the metastatic setting.

Induction therapy with chemotherapy with or without radiotherapy is an

established approach in stages II and III, however no data exist for induc-

tion therapy with TKI and chemotherapy in EGFR mt+ NSCLC. Here

we describe the outcome of 10 pts with EGFR mt+ NSCLC, all stage III,

treated with 1st and 3rd gen TKI in combination with chemotherapy as

induction therapy.

Methods: 10/10 pts had adenocarcinoma, 6 with EGFR exon 19 and 4 with

EGFR L858R. Pts received erlotinib (n=2), getinib (n=5) or osimertinib

(n=3) for 10 days followed by TKI in combination with chemotherapy

(docetaxel/cisplatin (n=5), paclitaxel/carboplatin (n=5)) for 3 cycles.

Results: 7/10 pts achieved radiologic PR aer 2 cycles, all tumors were

R0 resected. pCR was achieved in the primary tumor in 2/10, 5 pts did

not achieve pCR or MPR in the primary tumor. In the mediastinal lymph

nodes, MPR was achieved in 6/10 pts (1 pCR). 2 pts achieving pCR in the

primary tumor, 5 pts relapsed at 8 to 17 (median 12) months, 3/5 with

CNS as 1st relapse site and 2/5 with other sites. 3/10 pts have just started

therapy. With a median follow up of 46 months (13-68), 6 patients are

alive at 2+, 2+, 2+, 13+, 44+, 67+ months and one patient died in CR of

secondary cancer at 51 months. Median OS of the 10 pts was 51 months

and median PFS was 17 months.

Conclusion: In conclusion 1st and 3rd gen TKI-chemotherapy induction

in EGFR mt+ NSCLC is feasible, leads to high MPR rates in mediastinal

lymph nodes and lower pathologic response rates in the primary tumors.

pCR in the primary tumor may predict better outcome. As CNS is the

most frequent site of relapse this site might be of special interest in further

induction studies on EGFR mt+ NSCLC.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

706

Adherence to treatment recommendations from

multidisciplinary tumor boards

Julia Roeper1; Alice Blanksma1; Louis Kathmann1; Lena Ansmann2;

Frank Griesinger1

1Universitätsklinik Innere Medizin-Onkologie Universität Oldenburg, Pius

Hospital Oldenburg, Oldenburg, Deutschland

2Universität Oldenburg, Department für Versorgungsforschung,

Organisationsbezogene Versorgungsforschung, Oldenburg, Deutschland

Introduction: Lung cancer centers are responsible for coordinating the

care of lung cancer patients in a region and to diagnose and treat them

according to the latest evidence-based knowledge. In the tumor board an

individual treatment plan is discussed and treatment recommendations

are given. erefore, we investigate: 1.) how are the recommendations

from tumor boards being adhered to; 2.) which factors determine the

adherence of tumor board recommendations and 3.) what is the rela-

tionship between the adherence of tumor board recommendations and

patient outcomes in terms of OS?

Methods: Data from 1784 newly-diagnosed patients with lung cancer dis-

cussed in tumor boards in one certied lung cancer center in Northern

Germany between 2014 and 2018 were documented and evaluated accord-

ing to the adherence to tumor board recommendations. An analysis of the

rst 386 cases analyzed will be presented. Data was analyzed descriptively.

Results: Median age of the 386 patients was 66 years (26-91 yrs) and 64%

(n=247/386) of them were male. Most of the patients had an ECOG of 0

or 1 (78%; n=301/386) and 87% of them were current or ex heavy smoker

(n=335/386). In 79% (n=304/386) of patients, the treatment recommen-

dations from the multidisciplinary tumor boards were completely adhered

to. ere were dierent reasons for non-adherence, e.g. patient’s wish,

patient characteristics and death before starting therapy. e median OS

for the 386 patients was 13 months. Patients with a complete adherence

to the multidisciplinary tumor board recommendation had an OS of 16

months (n=304) compared to 5 months (n=41) for patients with a partial

adherence compared to 1 months (n=33) for patients with a non-adherent

treatment (p<0.001).

Conclusion: Preliminary results give a hint to the fact that patients with

an adherent treatment aer rst diagnosis had a longer overall survival

than patients with another therapy. More cases will be presented at the

meeting using a multivariate analysis which includes patient character-

istics and healthcare organizations that took over further treatment as

predictors.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts158

707

Real-world analysis of treatment and outcome for large-cell

neuroendocrine lung carcinoma

David Fisch1; Farastuk Bozorgmehr1; Daniel Kazdal2; Jonas Kuon3;

Laura Klotz4; Rajiv Shah1; Florian Eichhorn4; Mark Kriegsmann2;

Marc Schneider5; Albrecht Stenzinger2; Thomas Muley5; Helge G. Bischo1;

Michael Thomas1; Petros Christopoulos1

1Thoraxklinik Heidelberg , Abteilung für Thoraxonkologie, Heidelberg,

Deutschland

2Pathologisches Institut - Universitätsklinikum Heidelberg, Allgemeine

Pathologie und Pathologische Anatomie, Heidelberg,

3Thoraxklinik Heidelberg , Thoraxchirurgie, Heidelberg, Deutschland

4Thoraxklinik Heidelberg , Abteilung für Thoraxchirurgie, Heidelberg,

Deutschland

5TLRC – Translational Lung Research Center am Universitätsklinikum Heidelberg,

Heidelberg, Deutschland

Background: Large-cell neuroendocrine lung carcinoma (LCNEC) is a

rare pulmonary neoplasm with poor prognosis and limited therapeutic

options.

Methods: We retrospectively analyzed all patients with metastatic LCNEC

in the records of a large German academic center since 2010.

Result: 191 patients were identied with a predominance of male (68%)

smokers (92%) and a median age of 65 years. e single most import-

ant factor associated with outcome was the type of systemic treatment,

with a median overall survival (OS) of 26 months in case of immuno-

therapy (n=13), 9 months for other patients with rst-line platinum dou-

blets (n=129), and 4 months with non-platinum chemotherapies (n=17,

p<0.01). A lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008)

and fewer initial metastatic sites (HR 0.52, p=0.006) were independently

associated with longer OS, while the platinum drug type (cisplatin vs. car-

boplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smok-

ing status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA)

did not matter. 12% (23/191) of patients forewent systemic treatment,

mainly due to tumor-related clinical deterioration (n=13), while patient

refusal of therapy (n=5) and severe concomitant illness (n=5) were less

frequent. e attrition between successive treatment lines was approxi-

mately 50% and similar for platinum-based vs. other therapies, but higher

in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19%

(36/191) of patients had secondary stage IV disease and showed fewer

metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7

months, p=0.030).

Discussion: Highly active systemic therapies, especially immunotherapy

and platinum doublets, are essential for outcome in LCNEC and inuence

OS stronger than other disease parameters. e attrition between chemo-

therapy lines is ca. 50%. Patients with secondary metastatic disease have a

more favorable clinical phenotype and longer survival.

Conclusion: LCNEC shows considerable clinical heterogeneity, which

could be used for individualized management

Disclosure Statement: e authors declare no conict of interest.

712

Evaluation of the prognostic marker of PD-L1 expression after

combined radiochemotherapy in patients with non-small cell

lung cancer (NSCLC) stage III

Jan Wagner1; Julia Roeper1; Kay Willborn2; Frank Griesinger1

1Universitätsklinik Innere Medizin-Onkologie Universität Oldenburg,

PiusHospital Oldenburg, Oldenburg, Deutschland

2Pius Hospital Oldenburg

Background: e PACIFIC study showed that pts with locally advanced,

unresectable NSCLC aer radio-chemotherapy derived a benet in PFS

and OS when treated with durvalumab. In a post hoc analysis this eect was

limited to pts with a PD-L1 of >1%. In contrast, in pts with PD-L1 of <1%,

no benet was seen partly due to the fact that the outcome in the control

arm was surprisingly favorable. us, it could be speculated that lack of

PD-L1 expression confers a favorable outcome aer radio-chemotherapy

in stage III NSCLC. To address the question, whether the prolonged OS in

the control group with lack of PD-L1 expression was reproducible we ana-

lyzed the PFS and OS in a group of 99 pts with stage III NSCLC homoge-

neously treated with radio-chemotherapy similar as in the PACIFIC trial

and not progressing aer radio-chemotherapy.

Methods: Clinical data, tumor characteristics and outcome were system-

atically captured from the data base of the certied lung cancer center

Oldenburg, including the PD-L1-score. In cases, where the PD-L1 expres-

sion had not been evaluated, the available tissues samples were reanalyzed

for PD-L1 expression by Hematopathology Hamburg, aer informed con-

sent of the surviving pts had been obtained. For statistical analyses, log

rank test as well as multivariate analyses were performed.

Results: e study showed that the expression of PD-L1 is independent

from gender and histology. e median OS of the pts with an expression

of PD-L1 <1% was 20 months (KI 10.5 – 29.5) and with an expression ≥1%

28 months (KI 16.5 – 39.3), however this dierence was not statistically

signicant with a p-value of 0.734. e median PFS of pts with an expres-

sion of PD-L1 <1% was 9 months (KI 6.4 – 11.6) and with an expression

≥1% 12 months (KI 9.8 – 14.2), also not being statistically signicant with

a p-value of 0.112. e blood parameters serum CRP, albumin and CRP/

albumin-ratio had no signicant impact on OS.

Conclusion: is study showed that the assumption that lack of PD-L1

expression confers a favorable prognosis aer radio-chemotherapy vs.

PD-L1 expression >1% was not conrmed in our patient cohort.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

728

Predictive factors in the therapy of NSCLC with

pembrolizumab

Sonja Traubeck1; Amanda Tufman1; Diego Kaumann-Guerrero1

1LMU University Hospital Munich, Department of Internal Medicine

V - Pulmonology, Munich, Deutschland

Background: Pembrolizumab is used both as monotherapy and com-

bination therapy in the treatment of NSCLC. ough it has proven

eective in many patients, there is a lack of clinical parameters cor-

relating with therapy outcome. is study investigated immunologic

and patient- specic parameters among a cohort of patients treated with

pembrolizumab.

Methods: We analyzed a retrospective cohort of 115 NSCLC patients

diagnosed and treated with pembrolizumab monotherapy or IO-chemo

combination at a tertiary care lung cancer center between 2015 and 2021.

Patient data was extracted from electronic and paper-based clinical les.

Result: Our total cohort was predominantly male (58.8%), the mean age

was 64.8 years and 60.5% had adenocarcinoma histology. Patients who

underwent pembrolizumab monotherapy proved signicantly older, har-

bored higher PD-L1 expression, and showed poorer performance status.

Pre-therapeutic neutrophile and lymphocyte counts as well as neutro-

phile-to-lymphocyte ratio signicantly predicted PFS in patients with

monotherapy, but not in combination treatment. Furthermore, elevated

CRP, neutrophile counts, NLR, eosinophile-to-lymphocyte ratio, throm-

bocyte-to-lymphocyte ratio, and the systemic inammation index were

signicantly associated with poor OS in patients with monotherapy as

well as those treated with IO combination.

Discussion: New reliable predictive factors are needed to characterize

NSCLC patients who benet from pembrolizumab treatment. e results

of our analysis indicate that baseline characteristics as well as standard

blood counts could be promising markers. However, prospective cohorts

are needed to conrm our hypotheses generating results.

Conclusion: Clinical patient characteristics as well as routinely obtained

pre-therapeutic markers and scores can predict prognosis of NSCLC

patients treated with pembrolizumab. is might be a helpful and cost-ef-

fective tool to guide patient treatment.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 159

760

The expression of genetic variants of cytochrome CYP1A1

(m1, m2 and m4) and their association with increased risk of

lung cancer

Darko Katalinic1; Ivan Aleric1; Aleksandar Vcev1; Lilly Soerensen2

1Faculty of Dental Medicine and Health and Faculty of Medicine, J.J. Strossmayer

University, Osijek, Kroatien

2Department of Cancer Medicine, Oslo, Norwegen

Background: e cytochrome P450 superfamily metabolic enzymes

(P450) could have a possible role in lung cancer susceptibility. erefore,

it is important to dene the expression prole of P450 and to establish

their prognostic signicance in subjects with lung cancer. e aim of the

study was to assess the role of CYP1A1 genotype and the possible associ-

ation with the risk of lung cancer development.

Methods: e study was performed among 359 subjects (69% males and

31% females; mean age of 59.96±18.24 years) with diagnosis of stage IV

small-cell (24.6% of patients) and non-small cell lung cancer (75.4% of

patients) compared to 167 healthy subjects (72% males and 28% females;

mean age of 69.96±11.74 years). e distribution of polymorphisms

CYP1A1(m1), CYP1A1(m2) and CYP1A1(m4) were detected using

quantitative real-time polymerase chain reaction restriction fragmenth

length polymorphisms assay (qRT-PCR-RFLP).

Result: Distribution of genetic variants CYP1A1(m1) and CYP1A1(m2)

were found to be statistically signicant (p<0.001) (40.1% and 31.4%

among lung cancer subjects compared to 31.2% and 19.6% amoung

control subjects). No polymorphic CYP1A1 (m4) genetic varinats were

detected among all subjects. Statistical analysis showed signicant risk

limited to squamos cell lung carcinoma in subjects carring at least one m1

or m2 allele but not with subjects diagnosed with lung adenocarcinoma

or small-cel lung cancer.

Discussion: A signicant dierence amoung distribution of CYP1A1(m1)

and CYP1A1(m2) polymorphic varinats between lung cancer subjects

and healthy subjects has been shown. Additionally, the results indicate

that CYP1A1(m1) and CYP1A1(m2) polymorphic variants are associated

with development of squamos cell lung carcinoma, but not of lung adeno-

carcinoma or small-cel lung cancer.

Conclusion: e results of the study demonstrate association between

CYP1A1(m1) and CYP1A1(m2) genetic polymorphisms and signicant

risk of the squamos cell lung carcinoma development.

Disclosure Statement: e authors declare no conict of interest

868

Safety and ecacy outcomes with durvalumab after

sequential chemoradiotherapy (sCRT) in stage III,

unresectable NSCLC (PACIFIC-6)

Helge Bischo1; Marina Chiara Garassino2,3; Julien Mazieres4;

Martin Reck5; Christos Chouaid6; Laura Cove-Smith7; Talal Mansy8;

Maria R. Migliorino9; Angelo Delmonte10; José Garcia Sánchez11;

Luis Enrique Chara Velarde12; Reyes Bernabe13; Luis Paz-Ares14;

Ignacio Diaz Perez15; Nataliya Trunova15; Kayhan Foroutanpour15;

Corinne Faivre-Finn7; Niels Reinmuth16

1Thoraxklinik, Heidelberg, Deutschland

2Fondazione IRCCS Istituto Nazionale dei Tumori, Mailand, Italien

3Department of Hematology/Oncology, The University of Chicago, Chicago, USA

4Institut Universitaire du Cancer de Toulouse, Toulouse, Frankreich

5German Center for Lung Research, Grosshansdorf, Deutschland

6Service de Pneumologie, Centre Hospitalier Intercommunal de Créteil, Créteil,

Frankreich

7The Christie NHS Foundation Trust and Manchester University Hospitals

Foundation Trust, Manchester, Vereinigtes Königreich

8South Tees Hospitals NHS Foundation Trust, Middlesbrough, Vereinigtes

Königreich

9Oncology Unit, ASST-Monza, San Gerardo Hospital, Monza, Italien

10San Camillo-Forlanini Hospital, Rom, Italien

11Medical Oncology Department, Hospital Arnau de Vilanova, Fundación para el

Fomento de la Investigación Sanitaria i Biomédica de la Comunidad Valenciana

(FISABIO), Valencia, Spanien

12Hospital Universitario de Guadalajara, Guadalajara, Spanien

13Hospital Universitario Virgen del Rocio, Sevilla, Spanien

14Universidad Complutense, CiberOnc, CNIO and Hospital Universitario 12 de

Octubre, Madrid, Spanien

15AstraZeneca, Gaithersburg, USA

16Thoracic Oncology, Asklepios Fachkliniken München-Gauting, Gauting,

Deutschland

Background: In the ph 3 PACIFIC trial, durvalumab (durva) aer con-

current CRT (cCRT) signicantly improved survival in pts with Stage

III, unresectable NSCLC. As many pts are ineligible for cCRT, the ph 2

PACIFIC-6 trial aims to assess safety with durva aer sequential CRT

(sCRT).

Methods: Pts with ECOG PS ≤2 and no progression aer Pt-based sCRT

were enrolled to receive durva 1500mg IV q4w ≤24 mths or until progres-

sion, unacceptable toxicity or consent withdrawal. e primary endpoint

was safety/tolerability of durva, dened by the incidence of grade 3/4

possibly related AEs (PRAEs) occurring within 6 mths of treatment (Tx)

initiation. PFS, ORR and OS, were secondary endpoints.

Result: 117 pts were enrolled; 114 (97.4%) had PS 0/1 and 3 (2.6%) had PS

2. Median age was 68.0 years (65.8% were aged ≥65), 62.4% were male and

37.6%/50.4%/11.1% had Stage IIIA/B/C NSCLC. 98.3% had past/present

medical conditions, mostly vascular (59.0%), respiratory (53.8%) and met-

abolic (51.3%) disorders. Median Tx duration was 32.0 weeks (37.6% were

ongoing Tx at data cuto). In all, 94.9% of pts had any AEs and 76.9% had

PRAEs. 18.8% had grade 3/4 AEs and 4.3% had grade 3/4 PRAEs (1.7%

had grade 3/4 PRAE pneumonitis); all pts with grade 3/4 PRAEs had these

events occur within 6 mths (4.3%; 95% CI, 1.4–9.7). 21.4% and 16.2% had

AEs and PRAEs leading to Tx discontinuation, respectively; pneumonitis

was the most common PRAE leading to discontinuation (10.3%). 2 pts

(1.7%) had fatal AEs; 1 was a PRAE (pneumonitis). Ecacy outcomes are

listed in the table.

Ecacy outcomes All patients (N=117) PS 0/1 cohort (N=114)

Median PFS, mths (95% CI) 10.9 (7.3–15.6) 13.1 (7.4–16.7)

12-mth PFS, % (95% CI) 49.6 (39.5–58.9) 50.1 (39.9–59.5)

Median OS, mths (95% CI) 25.0 (25.0–NC) 25.0 (25.0–NC)

12-mth OS, % (95% CI) 84.1 (75.6–89.9) 84.6 (76.0–90.3)

Conrmed ORR, % (95% CI) 17.1 (11.1–25.8) 17.5 (11.4–26.4)

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts160

Conclusion: Durva aer sCRT had a similar safety prole to that observed

with durva aer cCRT in the PACIFIC trial and showed encouraging pre-

liminary ecacy in a frailer and older population.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

908

Durvalumab (D) ± tremelimumab (T) + platinum-etoposide

(EP) in 1L extensive-stage (ES) SCLC: characteristics of

long-term survivors in the CASPIAN study

Jonathan W Goldman1; Marina Chiara Garassino2; Yuanbin Chen3;

Katsuyuki Hotta4; Artem Poltoratskiy5; Maximilian J Hochmair6;

Mustafa Özgüroğlu7; Jun Ho Ji8; Galina Statsenko9; Oleksandr Voitko10;

Nikolay V Conev11; Igor Bondarenko12; Helen Mann13; Mingchao Xie14;

Yashaswi Shrestha15; Priti Chugh14; Tapashi Dalvi15; Luis Paz-Ares16;

Helge Bischo17

1David Geen School of Medicine at UCLA, Los Angeles, USA

2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italien

3Cancer & Hematology Centers of Western Michigan, Grand Rapids, USA

4Okayama University Hospital, Okayama, Japan

5Petrov Research Institute of Oncology, St. Petersburg, Russische Föderation

6Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik

Floridsdorf, Vienna, Österreich

7Istanbul University−Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul,

Türkei

8Samsung Changwon Hospital, Sungkyunkwan University School of Medicine,

Changwon, Republik Korea

9Omsk Regional Cancer Center, Omsk, Russische Föderation

10Kyiv City Clinical Oncological Centre, Kiev, Ukraine

11Clinic of Medical Oncology, UMHAT St Marina, Varna, Bulgarien

12Dnipropetrovsk Medical Academy, Dnipro, Ukraine

13AstraZeneca, Cambridge, Vereinigtes Königreich

14AstraZeneca, Waltham, USA

15AstraZeneca, Gaithersburg, USA

16Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit,

Universidad Complutense and Ciberonc, Madrid, Spanien

17Thoraxklinik Heidelberg gGmbH , University hospital Heidelberg, Heidelberg,

Deutschland

Background: In the Phase 3 CASPIAN trial, 1L D+EP signicantly

improved OS vs EP and OS benet was sustained aer >3 years median

follow-up (HR 0.71; 95% CI 0.60‒0.86; nominal p=0.0003). Here we assess

clinical and molecular characteristics of pts who experienced long-term

survival in CASPIAN.

Methods: 805 pts with ES-SCLC were randomised 1:1:1 to D+EP, D+T+EP

or EP. In post-hoc analyses, clinical characteristics were assessed in long-

term survivors (LTS; n=94), dened as pts still alive at the 22 Mar 2021

data cuto (DCO; median follow-up 39.4 mo). PD-L1 expression and tis-

sue tumour mutational burden (tTMB) were assessed in the biomarker

evaluable populations (BEPs) according to OS landmark (18 and 36 mo).

Results: ere were 44 (16%), 37 (14%) and 13 (5%) LTS in the D+EP,

D+T+EP and EP arms, respectively. LTS had slightly higher incidence

of some favourable prognostic factors at baseline; incidence of brain/

liver mets was lower among LTS vs ITT, although they still occurred

in some LTS. More LTS received ≥4 cycles EP than ITT, with a higher

median overall treatment exposure in the IO+EP arms. 46 (27 D+EP; 19

D+T+EP) LTS were ongoing D treatment at this DCO. ORR and 24-mo

PFS rates were higher for LTS vs ITT in the IO+EP arms. Rates of serious

AEs (SAEs) were similar in LTS and ITT. In the D+T+EP arm only, inci-

dence of PD-L1 expression on ≥1% of tumour cells (TC) or immune cells

(IC) (but not tTMB >10 mut/Mb) was enriched in pts with OS ≥18 mo

vs OS <18 mo; enrichment was maintained with OS ≥36 mo (data will be

presented).

Discussion & Conclusion: ere were >3 times as many LTS in the D+EP

arm vs the EP arm. LTS were more likely to have favourable prognos-

tic characteristics than ITT, although some LTS had brain/liver mets at

baseline. Notably, most LTS completed EP induction and, in both the

IO+EP arms, had substantially greater overall treatment exposure, as well

as achieving higher ORR and longer PFS, vs ITT. ere was no evidence

of cumulative toxicity based on SAEs.

Indication of source: Reinmuth, N. et al, ELCC 2022

Funding: AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

912

Clinical and Molecular Characteristics of small-scale ROS1

aberrations in non-small cell lung cancer patients

Moritz Glaser1; Cornelia von Levetzow1; Sebastian Michels1; Lucia

Nogova1; Marianna Katzenmeier1; Claudia Wömpner1; Jaqueline

Schmitz1; Elisabeth Bitter1; Inken Terjung1; Elke Passmann1; Diana

Schauer1; Anna Eisert1; Rieke Fischer1; Richard Riedel1; Jan-Phillip Weber1;

Sabine Hahne1; Sabine Merkelbach-Bruse2; Reinhard Büttner2;

JürgenWolf1; Matthias Scheer1

1University Hospital of Cologne, Department I of Internal Medicine, Köln,

Deutschland

2University of Cologne, Cologne Institute of Pathology, Köln, Deutschland

Background: Fusions in the ROS1 proto-oncogene are among the best

treatable genetic aberrations in Non-small cell lung cancer (NSCLC).

Besides the occurrence of solvent-front mutations (SFM) in acquired

resistance to targeted therapy, little is known about ROS1 aberrations

other than fusions. We analyzed molecular and clinical characteristics of

ROS1 mutations in NSCLC patients without activating ROS1 fusions or

SFMs.

Methods: Next-generation sequencing (NGS) was performed on tissue

samples from NSCLC patients within the National Network Genomic

Medicine (nNGM). Patients with activating ROS1 fusions detected by

uorescence in-situ hybridization (FISH) were excluded. We analyzed

the mutations’ frequencies and characteristics as well as co-occurring

mutations.

Result: Of 8072 patients analyzed by NGS between 2018 and 2021, 118

(1.5%) patients harbored ROS1 mutations. Most patients were male

(76.3%) and had adenocarcinoma histology (57.6%). e median age at

diagnosis amounted to 68 years. Nearly all of the patients (96.5%) had a

smoking history, amassing 40 pack-years on average. e most frequent

ROS1 mutations were transversions (53.6%), without dening a genomic

hotspot region. Besides TP53 mutations (61.0%), KRAS (25.4%), EGFR

(7.6%), PIK3CA and FGFR1-4 mutations (5.9% each) co-occurred most

frequently. In 12 (10.2%) patients, ROS1 mutation was the only detected

aberration.

Discussion: Our cohort opposites the clinical characteristics of patients

with ROS1 fusion regarding sex, smoking history, age, and histology.

Conclusion: Further research is warranted to characterize their biological

impact and their potential to act as a drug target.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 161

920

Five-year survival outcomes with nivolumab (NIVO) +

ipilimumab (IPI) vs chemotherapy (chemo) as rst-line

(1L) treatment for metastatic non-small cell lung cancer

(mNSCLC): Results from CheckMate 227

Martin Reck1; Julie R. Brahmer2; Jong-Seok Lee3; Tudor-Eliade Ciuleanu4;

Reyes Bernabe Caro5; Makoto Nishio6; Laszlo Urban7;

Clarisse Audigier-Valette8; Lorena Lupinacci9; Randeep Sangha10;

Luis Paz-Ares11; Hossein Borghaei12; Kenneth John O’byrne13;

Ravi G. Gupta14; Judith Bushong14; LI LI14; Steven I. Blum14; Laura Eccles14;

Suresh S. Ramalingam15

1Airway Research Center North, German Center for Lung Research, LungClinic,

Grosshansdorf, Deutschland

2Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins

Kimmel Cancer Center, Baltimore, MD, USA

3Seoul National University Bundang Hospital, Seongnam, Republik Korea

4Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and

Pharmacy Iulia Hatieganu, Cluj-Napoca, Rumänien

5Hospital Universitario Virgen Del Rocio, Instituto de Biomedicina de Seville,

Seville, Spanien

6Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo,

Japan

7Mátrai Gyógyintézet, Matrahaza, Ungarn

8Orientation Oncologique (pole14), Hôpital Sainte-Musse, Toulon, Frankreich

9Hospital Italiano de Buenos Aires, Buenos Aires, Argentinien

10Cross Cancer Institute, Edmonton, Kanada

11Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid,

Madrid, Spanien

12Fox Chase Cancer Center, Philadelphia, PA, USA

13Princess Alexandra Hospital, Translational Research Institute and Queensland

University of Technology, Brisbane, Australien

14Bristol Myers Squibb, Princeton, NJ, USA

15Winship Cancer Institute, Emory University, Atlanta, GA, USA

Background: In CheckMate 227 part 1 (NCT02477826), 1L NIVO + IPI

demonstrated long-term, durable survival benet vs chemo in patients

(pts) with mNSCLC regardless of PD-L1 expression level. Here we present

the longest reported follow-up (5 y) of a phase 3 trial of 1L combination

immunotherapy in mNSCLC.

Methods: Adults with tx-naïve stage IV/recurrent NSCLC, no known

EGFR/ALK alterations, and ECOG performance status ≤ 1 were enrolled.

Pts with tumor PD-L1 ≥ 1% were randomized 1:1:1 to NIVO (3 mg/kg

Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W), or chemo. Pts with

tumor PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO (360

mg Q3W) + chemo, or chemo. Pts were treated until progression, toxicity

or ≤ 2 y for NIVO±IPI. Assessments included overall survival (OS), pro-

gression-free survival (PFS), objective response rate (ORR), duration of

response (DOR), and tx-free interval (measured in pts who are o study tx

for any reason including treatment completion and dened as time from

last dose to start of subsequent systemic tx or death).

Results: Minimum follow-up was 61.3 mo (database lock: Feb 15, 2022).

In pts with tumor PD-L1 ≥ 1% (N = 1189), long-term OS benet contin-

ued with NIVO + IPI vs chemo (HR 0.77; 95% CI 0.66–0.91); 5-y OS rates

were 24% (NIVO + IPI) and 14% (chemo). OS benet also continued in

pts with tumor PD-L1 < 1% (N = 550) for NIVO + IPI vs chemo (HR 0.65;

0.52–0.81); 5-y OS rates were 19% (NIVO + IPI) and 7% (chemo). Clinical

benet with NIVO + IPI vs chemo was observed in the overall population

(5-y DOR rates, PD-L1 ≥ 1%: 28% vs 3%; PD-L1 < 1%: 21% vs not appli-

cable, NA) and in pts alive at 5 y (5-y DOR rates, PD-L1 ≥ 1%: 54% vs

17%; PD-L1 < 1%: 41% vs NA). OS, PFS, ORR and DOR with NIVO and

NIVO + chemo will be presented. Of pts alive at 5 y in the NIVO + IPI

arm, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were tx-free ≥ 3 y post-tx

discontinuation. No new safety signals were noted.

Conclusions: With a 5-y minimum follow-up, NIVO + IPI long-term,

durable clinical benet vs chemo is maintained for tx-naïve mNSCLC,

regardless of PD-L1 expression. NIVO + IPI increased 5-y survivorship;

most pts were tx-free for ≥ 3 y post-tx discontinuation.

permission. is abstract was accepted and previously presented at the

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

942

First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + 2

cycles of chemotherapy (chemo) vs chemo alone (4 cycles)

in patients (pts) with metastatic non-small cell lung cancer

(mNSCLC): 3-year update from CheckMate 9LA

Niels Reinmuth1; Luis Paz-Ares2; Tudor-Eliade Ciuleanu3;

Manuel Cobo-Dols4; Jaafar Bennouna5; Ying Cheng6; Hideaki Mizutani7;

Alejo Lingua8; Felipe Reyes9; Juliana Menezes10; Jacek Jassem11;

Svetlana Protsenko12; Kynan Feeney13; Emmanuel de la Mora Jimenez14;

Shun Lu15; Thomas John16; David Paul Carbone17; Xiaoqing Zhang18;

Nan Hu18; Martin Reck19

1Asklepios Lung Clinic Munich-Gauting, Gauting, Deutschland

2Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid,

Madrid, Spanien

3Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and

Pharmacy Iulia Hatieganu, Cluj-Napoca, Rumänien

4Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales

Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spanien

5University Hospital of Nantes and INSERM, CRCINA, Nantes, Frankreich

6Jilin Cancer Hospital, Changchun, China, VR

7Saitama Cancer Center, Saitama, Japan

8Instituto Medico Rio Cuarto SA, Córdoba, Argentinien

9Fundacion Arturo Lopez Perez, Santiago, Chile

10Hospital Nossa Senhora da Conceição, Porto Alegre, Brasilien

11Medical University of Gdańsk, Gdańsk, Polen

12N.N. Petrov National Medical Research Center of Oncology, St. Petersburg,

Russische Föderation

13St John of God Hospital Murdoch, Perth, Australien

14Instituto Jalisciense De Cancerología, Guadalajara, Mexiko

15Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong

University, Shanghai, China, VR

16Austin Hospital, Heidelberg, Australien

17The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

18Bristol Myers Squibb, Princeton, NJ, USA

19Airway Research Center North, German Center for Lung Research, LungClinic,

Grosshansdorf, Deutschland

Background: In CheckMate 9LA (NCT03215706), 1L NIVO + IPI com-

bined with 2 cycles of chemo was shown to provide survival benet vs

chemo alone in pts with mNSCLC. Here, we report updated ecacy and

safety with a 3-y minimum follow-up (f/u), as well as exploratory bio-

marker analyses.

Methods: Adults with stage IV/recurrent NSCLC, no known sensitizing

EGFR/ALK alterations, and ECOG performance status ≤ 1 were ran-

domized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + 2 cycles of

chemo (n = 361) or 4 cycles of chemo alone (n = 358). Pts were stratied

by tumor PD-L1 expression, sex, and histology. Pts with non-squamous

(NSQ) NSCLC in the chemo arm could receive pemetrexed maintenance.

Assessments included overall survival (OS), progression-free survival

(PFS), and objective response rate (ORR). For pts with NSQ NSCLC and

tissue evaluable for mutational analysis (n = 313), mutant (mut) or wild

type (wt) KRAS and STK11 genes were identied via the FoundationOne

CDxTM assay. Exploratory assessments included OS and PFS by mutation

status and safety.

Results: At a minimum f/u of 36.1 mo (database lock: Feb 15, 2022), pts

continued to derive long-term, durable OS benet with NIVO + IPI +

chemo vs chemo (HR 0.74 [95% CI 0.62–0.87]); 3-y OS rates were 27%

vs 19%. Clinical benet with NIVO + IPI + chemo vs chemo was also

observed across most subgroups, including by PD-L1 <1% (HR 0.67

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts162

[0.51–0.88]), PD-L1 ≥1% (HR 0.74 [0.60–0.93]) or histology. In an

exploratory analysis in pts evaluable for mutations, median OS appeared

improved with NIVO + IPI + chemo vs chemo (16.3 vs 13.1 mo). e

trend of prolonged median OS with NIVO + IPI + chemo vs chemo was

also seen in pts with/without KRAS mutation (mut: 19.2 vs 13.5 mo; wt:

15.6 vs 12.7 mo) or STK11 mutation (mut: 13.8 vs 10.7 mo; wt: 17.8 vs 13.9

mo), respectively. Additional ecacy outcomes will be presented. No new

safety signals were found with extended f/u.

Conclusions: With a 3-y minimum f/u, 1L NIVO + IPI + chemo demon-

strated long-term, durable ecacy benet vs chemo in pts with mNSCLC.

Survival benet of NIVO + IPI + chemo vs chemo was seen regardless of

KRAS and STK11 mutation status.

mission. is abstract was accepted and previously presented at the 2022

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

964

Evaluation of quality of life and survival time of lung cancer

patients treated in a certied German lung cancer center; a

real-world data study

Shiao Li Oei1; Anja Thronicke1; Hannah Wüstefeld2; Burkhard Matthes1,2;

Christian Grah2; Friedemann Schad1,3

1Forschungsinstitut am Gemeinschaftskrankenhaus Havelhöhe , Netzwerk

Onkologie, Berlin, Deutschland

2Gemeinschaftskrankenhaus Havelhöhe , Pneumologie , Onkologisches

Zentrum, Berlin, Deutschland

3Gemeinschaftskrankenhaus Havelhöhe , Interdisziplinäre Onkologie und

Palliativmedizin, Berlin, Deutschland

Background: Lung cancer (LC) is associated with high mortality and poor

quality of life (QoL) but due to advances in prognosis and treatments sur-

vival time is increasingly improving. e aim of this study was to analyze

associations between self-reported QoL and survival time in guide-line

treated LC patients in a real-world setting.

Methods: e real-world-data (RWD) study was conducted using

data from an oncological registry accredited by the German Cancer

Society. e study received positive ethics approval and was registered

(DRKS00013335 on 27/11/2017). Self-reported QoL of LC patients was

assessed by evaluation of the European Organization of Research and

Treatment Health-Related Quality of Life Core Questionnaire scale

(EORTC QLQ-C30). Association factors between QoL and survival time

were analyzed by adjusted multivariate linear regression analyses, using

the soware R.

Result: A total of 224 primary LC patients (all stages, median age 69 years)

answered QoL questionnaires at rst LC diagnosis and their dates of death

were documented. e median survival time of the entire study cohort

was 9.8 months (ICR: 4.7-17.5 months). Patients with early tumor stages,

if they could be surgically treated or undergo irradiation, or females sur-

vived signicantly longer. Among QoL parameters, a signicant associa-

tion was found between better self-reported nausea/vomiting scales and

prolonged survival (p=0.004), and similarly for appetite (p=0.03).

Discussion: QoL data and their impact on survival in LC patients are

poorly understood. Our results suggest that there may be a relevant asso-

ciation between certain QoL parameters self-reported at LC diagnosis and

survival time.

Conclusion: Our ndings suggest that nausea/vomiting and appetite

appear to be prognostic survival factors for LC patients.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

989

Cobolimab With Dostarlimab and Docetaxel in Patients (pts)

With Advanced Non-small Cell Lung Cancer (NSCLC): COSTAR

Lung

Hye Ryun Kim1; Cesare Gridelli2; Dinesh Kapur3; Amanda Tufman4;

Enriqueta Felip5; Vamsidhar Velcheti6; Yu Jung Kim7; Thorsten Götze8;

Pilar Garrido Lopez9; Romain Corre10; Konstantin Penkov11; Rana Anjum12;

Brian DI Pace12; Wenlei Liu12; Theo Borgovan12; Danielle Ledger12;

Jennifer Carver12; Angela Waszak12; Arindam Dhar12; Silvia Novello13

1Yonsei University College of Medicine

2S.G. Moscati Hospital

3Eastern Connecticut Hematology and Oncology

4Thoracic Oncology Centre Munich

5Vall d’Hebron University Hospital

6NYU Langone Health

7Seoul National University College of Medicine

8Institute of Clinical Cancer Research, Krankenhaus Nordwest, UCT University

Cancer Center

9Hospital Universitario Ramón y Cajal

10Centre Hospitalier Universitaire de Rennes

11Private Medical Institution Euromedservice

12GlaxoSmithKline

13University of Turin, San Luigi Hospital

Background: e Ph1 AMBER study (NCT02817633) showed that

cobolimab (GSK4069889, TIM-3 inhibitor) + dostarlimab (PD-1 inhib-

itor) had an acceptable safety prole in heavily pretreated, PD-1/PD-L1

relapsed/refractory (RR), advanced or metastatic NSCLC.

COSTAR Lung (NCT04655976) compares ecacy and safety of cobo-

limab + dostarlimab and SOC chemotherapy (CT, docetaxel; Arm A) to

dostarlimab + docetaxel (Arm B) to docetaxel (Arm C) in PD-1/PD-L1

RR NSCLC.

Methods: is is an ongoing global, multicenter, parallel-group treatment,

randomized, Ph2, open-label, 3-arm study, with potential Ph3 expansion.

Pts are ≥18 years, with advanced/metastatic NSCLC who received ≤2 prior

lines of therapy including anti-PD-1/PD-L1 therapy plus platinum-based

CT only. Other inclusion criteria include documented disease progression

(PD) on prior therapy, no sensitizing EGFR, ALK or ROS-1 mutations,

and ECOG PS 0–1.

Pts randomized 2:2:1 to Arms A, B, or C will receive cobolimab (300mg

IV), dostarlimab (500 mg IV), and/or docetaxel (75 mg/m2 IV) Q3W.

Cobolimab + dostarlimab will continue until PD, unacceptable toxicity,

withdrawal, investigator decision, or death. Docetaxel will continue for ≥4

cycles or until unacceptable toxicity or PD.

Primary endpoint: OS in Arms A or B vs C. Secondary endpoints: OS

in Arm A vs B and investigator-assessed conrmed objective response

rate (ORR); progression-free survival (PFS) and duration of response

(RECIST v1.1); quality of life assessments; safety; and tolerability.

Exploratory endpoints: investigator-assessed conrmed ORR and PFS

(iRECIST), pharmacokinetics, biomarkers of response, and pt-reported

ecacy/tolerability.

Result:

Discussion:

Conclusion: Approximately 250 pts will be randomized to Ph2 portion

with interim analysis planned aer ≥18 weeks follow-up; with an addi-

tional 500 pts (Arms A–B [n=200 each] and Arm C [n=100]) in Ph3

portion.

Funding: GSK (213410, NCT04655976). Previously presented at IASLC-

WCLC 2021 and submitted to DKK 2022 on behalf of original authors

with their permission.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 163

1007

Nintedanib in combination with nivolumab in pretreated

patients with advanced adenocarcinoma of the lung

(AIO-TRK-0117 Phase Ib/II trial)

Martin Sebastian1; Parvis Sadjadian2; Cornelius Waller3; Kato Kambartel4;

Christian Grohé5; Achim Rittmeyer6; Andrea Sendler7; Niels Reinmuth8;

Ralph Keller9; Hanna von Suchdoletz9; Martin Mänz9; Martin Reck10

1Universitätsklinikum Frankfurt Goethe Universität, Med. Klinik 2, Hämatologie/

Medizinische Onkologie, Frankfurt, Deutschland

2Universitätsklinik für Hämatologie, Onkologie, Hämostaseologie und

Palliativmedizin, Johannes Wesling Klinikum Minden, Universitätsklinikum der

Ruhr-Universität Bochum, Minden, Deutschland

3Universitätsklinikum Freiburg, Klinik für Innere Medizin I, Schwerpunkt

Hämatologie, Onkologie und Stammzelltransplantation, Freiburg, Deutschland

4Stiftung Bethanien Krankenhaus Moers, Klinik für Lungen- und

Bronchialheilkunde, Moers, Deutschland

5Evangelische Lungenklinik Berlin, Klinik für Pneumologie, Berlin, Deutschland

6Lungenfachklinik Immenhausen, Zentrum für Pneumologie, Immenhausen,

Deutschland

7Klinikum Hanau, Medizinische Klinik III, Hanau, Deutschland

8Asklepios Fachkliniken München-Gauting, Thorakale Onkologie, Gauting,

Deutschland

9AIO-Studien-gGmbH, Berlin, Deutschland

10LungenClinic Grosshansdorf, Thoraxonkologie, Deutsches Zentrum für

Lungenforschung. , Großhansdorf, Deutschland

Background: Nivolumab und Nintedanib sind etablierte Zweitlinien

therapien des nicht-plattenepithelialen NSCLC. NintNivo untersucht

das Potential einer Kombination der beidenerapieprinzipien in fort-

geschrittenen erapielinien des nicht-kleinzelligen Adenokarzinoms

derLunge

Methods: In der multizentrischen, oenen, einarmigen Phase Ib Studie

wurden Patient*innen (Pat) mit lokal fortgeschrittenem/metastasiertem

Adeno-NSCLC nach Versagen einer platinbasierten Chemotherapie

+/- Checkpointinhibitor (CPI) mit der Kombination Nintedanib und

Nivolumab behandelt. Nach einer klassischen Dosisndung im 3 +3

Design erhielten die Pat 200mg Nintedanib BID und 240mg Nivolumab

Q2W. Primäre Endpunkte waren Sicherheit, Verträglichkeit sowie pro-

gressionsfreies Überleben (PFS) nach 6 und 12 Monaten. Sekundäre

Endpunkte waren unter anderem die objektive Ansprechrate (ORR), PFS,

Gesamtüberleben (OS) und die Rate unerwünschter Ereignisse (AE).

Result: Im Phase 1b Teil zeigte sich keine dosislimitierende Toxizität sodass

53 Pat mit einem medianen Alter von 64 Jahren randomisiert wurden.

Die Mehrzahl erhielt in der Erstlinie eine platinhaltige Chemotherapie +/-

CPI, 15,1% erhielten zwei erapielinien vor Randomisierung. Die vorläu-

gne Ergebnisse zeigen eine ORR von 11,3% und eine stabile Erkrankung

bei 30,2% als bestes Ansprechen. Die PFS-Rate nach 6 und 12 Monaten

und das Gesamt-PFS waren 24.5% (95% CI, 14.0% bis 36.6%),10.5% (95%

CI 4.0% bis 20.8%) und 2.5 Monate. Die 1-Jahres OS-Rate war 53%, das

mediane OS 12,5 Monate. Behandlungsbedingte AEs fanden sich bei

86,6% der Pat, behandlungsbedingte AEs Grad 3 und höher bei 38,8%.

Conclusion: Unsere vorläugen Ergebnisse zeigen die Machbarkeit und

klinische Aktivität der Kombination von Nintedanib mit Nivolumab bei

Pat mit fortgeschrittenem/metastasierten Adenokarzinom der Lunge nach

Versagen einer Erstlinientherapie. Weitere Analysen und translationale

Untersuchungen untersuchen welche Pat von dieser erapie protieren.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1047

Pembrolizumab Maintenance Following First-Line Platinum

Based Chemotherapy in Patients with Metastatic Squamous

Non-Small Cell Lung Cancer (sqNSCLC) – AIO-TRK-0115/

PRIMUS

Parvis Sadjadian1; Jens Kollmeier2; Jens Kern3; Petra Hoknecht4;

Martin Sebastian5; Amanda Tufman6; M Maenz7; Martin Reck8

1Johannes Wesling Klinikum Minden, Universitätsklinik für Hämatologie,

Onkologie, Gerinnungsstörungen und Palliativmedizin, Minden,

2Helios Klinikum Emil von Behring Berlin

3Klinikum Würzburg Mitte Missioklinik

4Franziskus Hospital Harderberg, Georgsmarienhütte

5Universitätsklinikum Frankfurt

6LMU Universitätsklinik München

7AIO Studien gGmbH Berlin

8LungenClinic Grosshansdorf

Purpose: To improve outcomes for patients with advanced squamous

NSCLC, the phase II multi-center, double-blind PRIMUS trial was con-

ducted to explore the potential of pembrolizumab maintenance treatment

aer platinum-based induction chemotherapy.

Methods: Stage IV squamous NSCLC patients with least stable disease

aer at least 2 cycles of rst-line platinum-based chemotherapy were

randomized 1:1 to Q3W pembrolizumab maintenance treatment or

placebo, irrespective of tumor PD-L1 expression, for a maximum of 2

years. Primary endpoint was progression-free survival (PFS), secondary

endpoints included objective response rate (ORR), overall survival (OS),

PD-L1 expression in tumor samples, safety and tolerability, and quality of

life by FACT-L and LCSS questionnaires.

Results: Planned patient enrollment of 65 per arm was not met due

to changes of clinical treatment standards for rst-line treatment.

Pembrolizumab maintenance was administered to 16 patients, 18 patients

received placebo. Survival results favor Pembrolizumab maintenance

over placebo: Median PFS was 9.5 mo [95% CI 1.5-23.5] vs 4.8 mo [95%

CI 1.8-10.5]. PFS rate at 6, 12 and 18 months was 50.3% [95% CI 23.1-

72.4%], 35.9% [95% CI 13.1-59.6%] and 35.9% [95% CI 13.1-59.6%] vs

36.1% [95% CI 15.0-57.9%], 18.1% [95% CI 4.5-39.0%] and 9.0% [95% CI

0.7-30.9%]. Median OS was 24.0 mo [95% CI 9.5-30.9] vs 10.9 mo [95%

CI 4.8-39.2]. OS rates at 6 and 12 months were 86.7% [95% CI 56.4-96.5%]

and 79.4% [95% CI 48.8-92.9%] vs 69.3% [95% CI 41.1- 85.9] and 44.1%

[95% CI 20.0-65.9%]. AEs ≥ grade 3 potentially related to Pembrolizumab

according to investigator assessment occurred in 4 patients: grade 3

hyperthyreosis, myocarditis, nephritis and acute renal failure, and grade 4

bronchopulmonary hemorrhage.

Conclusion: Our results indicate a notable benet of the pembrolizumab

maintenance strategy compared to placebo in terms of survival. is is a

remarkable nding given that the number of treated patients was consid-

erably lower than planned. Further exploration is warranted.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts164

Lymphoma and Plasma Cell Disorders

Best-of-Abstract-Vortrag

891

Polatuzumab vedotin plus rituximab, cyclophosphamide,

doxorubicin, and prednisone (pola-r-chp) versus rituximab,

cyclophosphamide, doxorubicin, vincristine and prednisone

(r-chop) therapy in patients with previously untreated diuse

large b-cell lymphoma (dlbcl): results from the phase iii

polarix study

sascha Dietrich1; Hervé Tilly2; Franck Morschhauser3; Laurie H. Sehn4;

Jonathan W. Friedberg5; Marek Trněný6; Je Sharman7; Charles Herbaux8;

John M. Burke9; Matthew Matasar10; Shinya Rai11; Koji Izutsu12; Neha

Mehta-Shah13; Lucie Oberic14; Adrien Chauchet15; Wojciech Jurczak16;

Yu Qin Song17; Richard Greil18; Larysa Mykhalska19;

Juan Miguel Bergua Burgués20; Matthew C. Cheung21; Antonio Pinto22;

Ho-Jin Shin23; Greg Hapgood24; Eduardo Munhoz25; Gilles Salles26

1Klinik für Hämatologie, Onkologie, Rheumatologie, Universitätskilinikum

Heideberg, Heidelberg, Deutschland

2Centre Henri Becquerel and University of Rouen, Rouen, Frankreich

3Univ. Lille, CHU Lille, Group de Recherche sur les formes Injectables et les

Technologies Associées, Lille, Frankreich

4BC Cancer Centre for Lymphoid Cancer and the University of British Columbia,

Vancouver, Kanada

5UR Medicine – Wilmot Cancer Center, Rochester, USA

6First Faculty of Medicine, Charles University, General Hospital, Prag, Tschechien

7Willamette Valley Cancer Institute/US Oncology, Eugene, USA

8CHU de Montpellier, Montpellier, Frankreich

9Rocky Mountain Cancer Centers/US Oncology, Aurora, USA

10Memorial Sloan Kettering Cancer Center, New York City/Montvale, USA

11Kindai University, Faculty of Medicine, Osaka-Sayama City, Japan

12National Cancer Center Hospital, Tokyo, Japan

13Washington University in St. Louis, St. Louis, USA, MO

14Institut Universitaire du Cancer, Toulouse-Oncopole, Toulouse, Frankreich

15Department of Hematology, CHRU Besançon, Besançon, Frankreich

16Maria Sklodowska – Curie National Research Institute of Oncology, Kraków,

Polen

17Peking University Cancer Hospital, Beijing

18Paracelsus Medical University, Salzburg Cancer Research Institute-CCCIT and

Cancer Cluster Salzburg, Salzburg, Österreich

19Clinical Hospital Feofaniya, Kyiv, Ukraine

20Hospital San Pedro de Alcántara, Cáceres, Spanien

21Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of

Toronto, Toronto, Kanada

22Hematology-Oncology & Stem Cell Transplantation Unit, Istituto Nazionale

Tumori, Fondazione ‘G. Pascale’, IRCCS, Naples, Italien

23Medical Research Institute, Pusan National University Hospital, Pusan National

University School of Medicine, Busan, Südkorea

24Princess Alexandra Hospital, Brisbane, Australien

25Hospital Erasto Gaertner, Curitiba, Brasilien

26Memorial Sloan Kettering Cancer Center, New York City, USA

Background: R-CHOP is standard of care for newly diagnosed DLBCL

patients (pts), yet 40% remain uncured. Polatuzumab vedotin, a CD79b-

targeting antibody-drug conjugate, has shown promising activity in a

Phase Ib/II study. We report POLARIX (NCT03274492), a double-blind,

placebo-controlled, international Phase III study comparing Pola-R-CHP

vs R-CHOP in treatment-naïve DLBCL pts with an IPI score of 2–5.

Methods: Pts were randomised (1:1) to 6 cycles of Pola-R-CHP or R-CHOP.

On day 1 of cycles 1–6, pts received polatuzumab vedotin 1.8mg/kg or

vincristine 1.4mg/m² + rituximab 375mg/m2, cyclophosphamide 750mg/

m², and doxorubicin 50mg/m². Pts also received oral prednisone 100mg

on days 1–5 and two further cycles of rituximab. Investigator-assessed PFS

was the primary endpoint.

Result: Overall 879 pts (median age 65 [range 19–80] years) were ran-

domised (Pola-R-CHP: n=440; R-CHOP: n=439). At primary data cut-o

(28 June 2021), median follow-up was 28.2 months. PFS was superior

(HR 0.73; 95% CI: 0.57–0.95; P=0.02) and 2-year PFS rate was improved

(76.7% [95% CI: 72.7–80.8] vs 70.2% [95% CI: 65.8–74.6]) with Pola-

R-CHP vs R-CHOP. EFS favoured Pola-R-CHP vs R-CHOP (HR 0.75

95% CI: 0.58–0.96; P=0.02). While end-of-treatment PET-CT CR

rate was not signicantly dierent with Pola-R-CHP (78.0%) vs

R-CHOP (74.0%), DFS suggested more durable responses (HR 0.70

95% CI: 0.50–0.98). OS was comparable between treatment arms. Similar

safety proles were seen between treatment groups. For Pola-R-CHP vs

R-CHOP, rates of grade 3–4 adverse events (AEs) were 57.7% vs 57.5%,

serious AEs were 34.0% vs 30.6%, grade 5 AEs were 3.0% vs 2.3%, and

AEs leading to dose reduction were 9.2% vs 13.0%, respectively. Rates of

peripheral neuropathy were similar for Pola-R-CHP vs R-CHOP. At data

cut-o, fewer pts treated with Pola-R-CHP (23%) vs R-CHOP (30%) had

received ≥1 subsequent anti-lymphoma therapy.

Conclusion: As rst-line treatment of DLBCL, Pola-R-CHP demon-

strated a 27% reduction in relative risk of disease progression, relapse, or

death, and a similar safety prole, vs R-CHOP.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

967

Phase 3 TRANSFORM study of lisocabtagene maraleucel

(liso-cel), a CD19-directed chimeric antigen receptor

T cell therapy (Tx), versus standard of care (SOC) of

salvage chemotherapy followed by autologous stem cell

transplantation (ASCT) as second-line (2L) Tx in patients (pt)

with relapsed or refractory (R/R) large B-cell lymphoma (LBCL)

Bertram Glaß1; Manali Kamdar2; Scott Solomon3; Jon Arnason4;

Patrick B Johnston5; Sami Ibrahimi6; Stephan Mielke7; Pim Mutsaers8;

Francisco Hernandez-Ilizaliturri9; Koji Izutsu10; Franck Morschhauser11;

Matthew Lunning12; David Maloney13; Alessandro Crotta14;

Sandrine Montheard14; Alessandro Previtali14; Lara Stepan15;

Ken Ogasawara15; Jeremy Abramson16

1Helios Klinikum Berlin-Buch, Berlin, Deutschland

2University of Colorado Cancer Center, Colorado, USA

3Northside Hospital Cancer Institute, USA

4Beth Israel Deaconess Medical Center, Boston, USA

5Mayo Clinic, Rochester, USA

6University of Oklahoma Stephenson Cancer Center, Oklahoma, USA

7Center of Allogeneic Stem Cell Transplantation and Cellular Therapy (CAST),

Karolinska Institutet and University Hospital, Solna, Schweden

8Erasmus University Medical Center, Rotterdam, Niederlande

9Roswell Park Comprehensive Cancer Center, New York, USA

10National Cancer Center Hospital, Singapur, Japan

11Université de Lille, Centre Hospitalier Universitaire de Lille. ULR 7365, GRITA –

Groupe de Recherche sur les formes Injectables et les Technologies Associées,

Lille, Frankreich

12University of Nebraska Medical Center, Nebraska, USA

13Fred Hutchinson Cancer Research Center, Seattle, USA

14Celgene, a Bristol-Myers Squibb Company, Zürich, Schweiz

15Bristol-Myers Squibb, Seattle, USA

16Massachusetts General Hospital Cancer Center, Massachusetts, USA

Background: We present a prespecied interim analysis comparing the

investigational CD19-directed CAR T cell product, liso-cel (Arm B), with

SOC (Arm A) as 2L Tx in pts with R/R LBCL in the randomized phase 3

TRANSFORM study (NCT03575351; Kamdar M, et al. in press).

Methods: Pts with LBCL primary refractory to or relapsed ≤12 mo aer

rst-line Tx received liso-cel or SOC (3 cycles of R-DHAP, R-ICE, or

R-GDP, then BEAM+ASCT in responders). Pts were aged 18–75 years

and intended for transplant, with ECOG PS ≤1 and adequate organ

function; secondary CNS lymphoma was allowed. Bridging Tx with an

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 165

SOC regimen was allowed for disease control during liso-cel manufactur-

ing. Primary endpoint was EFS, with response assessed by Independent

Review Committee per Lugano 2014 criteria. Key secondary endpoints

included CR rate, PFS, and OS.

Result: Baseline characteristics were balanced between the 92 pts ran-

domized to each arm. In Arm B, 90 pts received liso-cel infusion; 58 pts

(63%) received bridging Tx. Median follow-up was 6.2 mo (range, 0.9–

20.0). Median EFS was signicantly longer for liso-cel versus SOC (10.1

mo vs 2.3 mo; HR, 0.349; 95% CI, 0.229–0.530; P<0.0001). CR rate and

PFS showed statistically signicant improvements for Arm B. In Arm B,

any-grade cytokine release syndrome (CRS) was reported in 49% of pts;

only 1 pt had grade 3 CRS and 0 had grade 4/5. Any-grade neurological

events were reported in 12% of pts and were primarily low grade (grade

3, 4%; grade 4/5, 0%). In Arm B, 24% of pts received tocilizumab, 17%

received corticosteroids, and none received vasopressors. e most com-

mon treatment-emergent AEs in both arms were cytopenias.

Discussion: In TRANSFORM, liso-cel demonstrated statistically signi-

cant and clinically meaningful improvement in EFS compared with SOC

as 2L Tx. No new liso-cel safety concerns were identied.

Conclusion: Liso-cel improved outcomes versus SOC and exhibited a

favorable safety prole, providing support for liso-cel as a standard 2L Tx

in LBCL.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Poster

150

Pomalidomide (POM), bortezomib (BORT), and

dexamethasone (DEX) after 1 prior line of therapy in relapsed

or refractory multiple myeloma (RRMM): a safety subanalysis

of the phase 3 OPTIMISMM trial

Katja Weisel1; Meletios Dimopoulos2; Albert Oriol3; Meral Beksac4;

Frederick Schjesvold5; Anna Marina Liberati6; Jindriska Lindsay7;

Darrell White8; Jésus San-Miguel9; Philippe Moreau10;

Larry D. Anderson Jr11; Alessandra Lorocca12; Pawel Robak13; Prisca

Vogel14; Ruiyun Jiang15; Lara Grote15; Teresa Peluso14; Paul Richardson16

1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

2National and Kapodistrian University of Athens, Athens, Griechenland

3Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Josep Carreras

Leukaemia Research Institute, Badalona, Spanien

4Ankara University, Ankara, Türkei

5Oslo Myeloma Center, Oslo University Hospital and KG Jebsen Center for B-cell

malignancies, University of Oslo, Oslo, Norwegen

6University of Perugia, Perugia, Italien

7East Kent Hospitals University NHS Foundation Trust, Kent and Canterbury

Hospital, Canterbury, Vereinigtes Königreich

8Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax,

Kanada

9Clinica Universidad de Navarra, Pamplona, Spanien

10University Hospital Hôtel-Dieu, Nantes, Frankreich

11UT Southwestern Medical Center, Dallas, USA

12A.O.U. Citta Della Salute e della Scienza di Torino, Torino, Italien

13Department of Hematology, Medical University of Lodz, Copernicus Memorial

Hospital, Ciolkowskiego, Polen

14Celgene International Sàrl, a Bristol Myers Squibb Company, Boudry, Schweiz

15Bristol Myers Squibb, Princeton, USA

16Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology,

Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA

Background: Patients (pts) with newly diagnosed multiple myeloma

(MM) are routinely treated with lenalidomide (LEN) until disease pro-

gression, thus frequently developing LEN-refractory MM at relapse. Pts

with RRMM treated with POM, BORT, and DEX (PVd) at rst relapse in

OPTIMISMM (phase 3, NCT01734928) had a signicantly longer median

progression-free survival (20.7 vs 11.6 mo) vs BORT and DEX (Vd); all

pts were LEN-exposed and 57% were LEN refractory (Richardson et al.

Lancet Oncol 2019;20:781–94). Here we report a safety analysis of treat-

ment-emergent adverse events (TEAE) in the events of interest (EOI) cat-

egory for PVd vs Vd administered at rst relapse in OPTIMISMM.

Methods : In 21-day cycles, pts with RRMM received PVd or Vd (1:1).

Key eligibility criteria included ≥ 2 cycles of prior LEN; LEN-refractory

pts were allowed. AEs were graded (NCI CTCAE v4.0) and summarized

by system organ class and preferred term.

Result: e safety analysis included 221/559 pts (PVd, n = 111; Vd, n =

110) who had 1 prior line of therapy and received ≥ 1 dose of study drug.

Median duration of treatment was longer in the PVd vs Vd arm: 47.4 vs

27.1 weeks. e most common grade (Gr) 3/4 TEAE EOIs were neutrope-

nia (24.4%), infections and infestations (22.2%), and thrombocytopenia

(20.4%). Gr 3/4 TEAE EOIs more common in the PVd vs Vd arm included

neutropenia (36.9% vs 11.8%), infections and infestations (28.8% vs

15.5%), and peripheral neuropathy (PNP; 11.7% vs 4.5%). Onset of TEAE

EOIs were mostly in early cycles and mainly managed with dose reduc-

tions/interruptions. POM discontinuations due to ≥ 1 TEAE EOI of any

grade were low (9.0%). Infections and infestations were the primary cause

of PVd dose interruptions (54.1%). PNP was the most common TEAE

EOI leading to dose reduction (32.4%) and drug discontinuation (16.2%)

with PVd.

Discussion: e safety prole of PVd at rst relapse in pts with RRMM

aligns with previous reports.

Conclusion: TEAE EOIs generally occurred in early treatment cycles and

were manageable with dose modications or appropriate treatment.

Source:

1. Weisel K, et al. HemaSphere 2021;5:e464–5. EP988

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

166

Acalabrutinib ± Obinutuzumab vs Obinutuzumab +

Chlorambucil in Treatment-Naive Chronic Lymphocytic

Leukemia: 5-Year Follow-Up of ELEVATE-TN

Uwe Martens1; Je Sharman2; Miklos Egyed3; Wojciech Jurczak4;

Alan P. Skarbnik5; Manali Kamdar6; Talha Munir7; Laura Maria Fogliatto8;

Yair Herishanu9; Versha Banerji10; George Follows11; Patricia Walker12;

Karin Karlsson13; Paolo Ghia14; Ann Janssens15; Emmanuelle Ferrant16;

Veerendra Munugalavadla17; Ting Yu17; Min Hui Wang17;

Jennifer Woyach18

1SLK-Kliniken GmbH Heilbronn, Heilbronn, Deutschland

2Willamette Valley Cancer Institute and Research Center, Eugene, OR, USA

3Somogy County Mór Kaposi General Hospital, Kaposvár, Ungarn

4Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Polen

5Novant Health Cancer Institute, Charlotte, North Carolina, USA

6University of Colorado Cancer Center, Aurora, Colorado, USA

7Haematology, Haematological Malignancy Diagnostic Service (HMDS), St.

James’s Institute of Oncology, Leeds, Vereinigtes Königreich

8Hospital de Clinicas de Porto Alegre, Porto Alegre, Brasilien

9Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

10University of Manitoba and CancerCare Manitoba, Winnipeg, MB, Kanada

11Department of Haematology, Addenbrooke’s Hospital NHS Trust, Cambridge,

Vereinigtes Königreich

12Peninsula Health and Peninsula Private Hospital, Frankston, Melbourne,

Australien

13Skåne University Hospital, Lund, Schweden

14Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,

Italien

15University Hospitals Leuven, Leuven, Belgien

16Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’Hématologie

Clinique, Pierre-Bénite, Frankreich

17AstraZeneca, South San Francisco, CA, USA

18The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

Background: For ELEVATE-TN (NCT02475681), we previously reported

superior ecacy of acalabrutinib (A) ± obinutuzumab (O) vs O + chlo-

rambucil (Clb) in patients (pts) with treatment-naive (TN) chronic

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts166

lymphocytic leukemia (CLL) at 28.3 and 46.9 months (mo) median fol-

low-up. As submitted to ASCO 2022, we now report results from a 5-year

(y) update.

Methods: Pts were randomized to A+O, A, or O+Clb. Pts who progressed

on O+Clb could cross over to A monotherapy. Investigator-assessed

(INV) progression-free survival (PFS), INV overall response rate (ORR),

overall survival (OS), and safety were evaluated.

Result: A total of 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) had a

median age of 70 y. At a median follow-up of 58.2 mo (range, 0.0–72.0;

data cuto Oct 1, 2021), median PFS was not reached (NR) (hazard

ratio [HR]: 0.11) for A+O and A (HR: 0.21) vs 27.8 mo for O+Clb (both

P<0.0001). Estimated 60-mo PFS rates were 84% (A+O), 72% (A), and

21% (O+Clb). Median OS was NR in any treatment arm, and signicantly

longer in the A+O vs O+Clb arms (HR: 0.55; P=0.0474); estimated 60-mo

OS rates were 90% (A+O), 84% (A), and 82% (O+Clb). ORR was signi-

cantly higher with A+O (96%; 95% CI 92–98) and A (90%; 85–94) vs

O+Clb (83%; 77–88; P<0.0001 [A+O], P=0.0499 [A]). Complete response

(CR)/ CR with incomplete hematologic recovery (CRi) rates were higher

with A+O (29%/3%) vs O+Clb (13%/1%); 13%/1% had CR/CRi with

A; CR increased since the interim analysis (previously 21% [A+O] and

7% [A]). Treatment is ongoing in 65% (A+O) and 60% (A) of pts; the

most common reasons for treatment discontinuation were adverse events

(AEs) (17% [A+O], 16% [A], 14% [O+Clb]) and progressive disease (6%,

10%, 2%, respectively). Crossover from O+Clb to A occurred in 72 (41%)

patients; 25% of these pts discontinued A (10% due to AEs and 11% due

to progressive disease).

Discussion and Conclusion: Aer a 5-y follow-up, ecacy and safety of

A+O and A monotherapy were maintained, with signicantly longer OS

in the A+O arm compared with O+Clb.

Sponsor: Acerta Pharma BV; AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

239

Eectiveness and Safety of Sandoz Biosimilar Rituximab

(Rixathon [c]) in Patients with DLBCL: 24-Month Evidence from

the REFLECT Study

Manfred Welslau1; Thomas Wol2; Burkhard Joerg Otremba3;

Julian Topaly4; Boris Kubuschok5; Galyna Bryn6

1Chefarzt MK IV - Klinikum Aschaenburg, Aschaenburg, Deutschland

2Onkologie Lerchenfeld, Hamburg, Deutschland

3Onkologische Praxis, Oldenburg-Delmenhorst, Oldenburg, Deutschland

4MVZ Klinikum Osnabrück GmbH, Osnabrück, Deutschland

5Medizinische Klinik und Comprehensive Cancer Center, Universitätsklinikum

Augsburg Stenglinstr, Augsburg, Deutschland

6Sandoz Group, a Novartis Division, Holzkirchen, Deutschland

Background: Sandoz rituximab (SDZ-RTX; Rixathon®), a biosimilar,

was approved in Europe for all indications of the reference rituximab.

REFLECT is a real-world, multicentre non-interventional trial and is the

rst prospective post-approval study of SDZ-RTX in combination with

CHOP as curative therapy for diuse large B-cell lymphoma (DLBCL).

Objective: To evaluate the 2-year eectiveness and safety of SDZ-RTX

in 1st line treatment of DLBCL. Eectiveness was measured by complete

response (CR) rate as primary endpoint.

Methods: Treatment-naïve, CD20+ adult patients (aged ≥18 years) with

DLBCL, eligible for therapy with rituximab-CHOP were treated with

SDZ-RTX-CHOP every 2 to 3 weeks for 6–8 cycles according to product

label. CR was assessed as the best result by the treating physician.

No imputation for missing data was used; endpoints were summarized

descriptively.

Results: A total of 169 patients (52.1% women, mean [SD] age 67.3 [13.4]

years) with DLBCL were included. At baseline most patients (80.5%) had

an Eastern Cooperative Oncology Group (ECOG) performance score of

0/1. A total of 100 (59.2%) patients completed the 24-month observation

period. Overall response was achieved in 160 (94.7%) patients (95%CI:

90.1–97.5). A majority, 110 (65.1%) patients, achieved CR (95%CI:

57.4–72.3) and 50 (29.6%) patients achieved partial response (95%CI:

22.8–37.1). One year progression free survival (PFS) was 84.9% (95%CI:

78.2–89.6), while 2 years PFS was 78.5% (95%CI: 70.9–84.4). Median PFS

was not reached. A total of 143 (84.6%) patients experienced at least one

AE; most common were anaemia (24.3%), fatigue (20.7%), polyneuropa-

thy (17.2%) and nausea (12.4%).

Conclusion: is study reconrms that 1st line treatment of CD20+

DLBCL with R-CHOP using SDZ-RTX (Rixathon [c]) is eective over a

24-months observation period with no unexpected safety signals.

Disclosure Statement: e authors declare the following:

1. Manfred Welslau: Dr. Welslau reports engagement other from Novartis, during

the conduct of the study; consultation to AMGEN, Bristol-Myers Squibb,

Celgene, GILEAD, HEXAL, Janssen, Lilly, medac, Roche, SANOFI, and

received honorariums from AMGEN, astellas, AstraZeneca, Celgene, GILEAD,

HEXAL, Janssen, Lilly, Roche, SANOFI, outside the submitted work.

2. Galyna Bryn: Dr. Bryn is employed by Sandoz, during the conduct of the study.

252

Final results of IDELA PASS: A prospective non-interventional

post authorization safety study of idelalisib in Germany

Manuela Hoechstetter1; Wolfgang Ulrich Knauf2; Silvia Dambacher3;

Nike Hucke3; Anna van Troostenburg3; Heribert Ramroth3;

Wolfgang Abenhardt4; Mathias Rummel5

1München Klinik Schwabingen, Klinik für Hämatologie, Onkologie,

Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin, München,

Deutschland

2Onkologie Bethanien Frankfurt am Main, Centrum für Hämatologie und

Onkologie, Frankfurt am Main, Deutschland

3Gilead Sciences GmbH, Martinsried bei München, München, Deutschland

4Onco Consult Gilching GmbH, Gilching, Deutschland

5Universitätsklinikum Gießen und Marburg, Schwerpunktabteilung für

Hämatologie (Med. Klinik IV), Gießen, Deutschland

Background: In clinical studies idelalisib (rst-in-class PI3Kδ-inhibitor)

demonstrated signicant ecacy in patients with CLL and FL. On this

basis idelalisib is indicated in combination with rituximab for the treat-

ment of adult patients with chronic lymphocytic leukaemia (CLL) who

received at least one prior therapy or as 1L treatment in the presence of

del(17p) or TP53mut in patients not eligible for any other therapy and as

monotherapy for the treatment of adult patients with follicular lymphoma

(FL) refractory to two prior lines of treatment. Here we show the nal

results of Post-Authorization Safety Study (PASS) prospectively investi-

gating safety and eectiveness in routine clinical practice in Germany.

Methods: A prospective, two-cohort, multicenter, PASS reporting safety

and eectiveness. Inclusion of patients was based on the physician’s deci-

sion and in accordance with the European SmPC. Descriptive statistics

were used for data analysis.

Result: is nal analysis shows data from 147 patients (125 CLL; 22

FL) with a median age of 74 (43-92) years. Most patients presented with

≥one comorbidity and advanced disease status at baseline. With a median

observation time of 9.2 (7.0-11.3) months the median OS was not reached

(NR) for either patient population including CLL patients with and with-

out del(17p) and/or TP53mut. In patients with CLL the ORR was 70%, for

FL 36%. Median PFS for FL was 3.5 (2.3 – 7.7) months, whereas NR for

CLL. Subgroup analysis in the CLL cohort of PFS by numbers of prior reg-

imens suggests that idelalisib treatment in earlier lines of therapy results

in a longer PFS. e most frequently reported ADR in CLL and FL cohort

was diarrhoea with 28%/36.4%.

Discussion: Real-world eectiveness in this PASS conrms clinical e-

cacy of idelalisib in CLL. e collected safety data and the pattern of ADRs

in this study reect the patterns of ADRs from previous clinical trials with

idelalisib.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 167

Conclusion: e results demonstrate that idelalisib is a potent treatment

for patients with CLL and FL with a manageable safety prole in routine

clinical practice.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

339

PET-Guided Treatment in Patients with Early-Stage Favorable

Hodgkin Lymphoma: Follow-up Analysis of the HD16 Trial by the

German Hodgkin Study Group

Anne Sophie Jacob1; Michael Fuchs1; Helen Kaul1; Carsten Kobe2;

Thomas Pabst3,4; Richard Greil5,6; Dennis Eichenauer1; Max Topp6;

Marianne Just7; Bernd Hertenstein8; Valdete Schaub9;

Martin Vogelhuber10; Josée M Zijlstra11; Annette Pluetschow1;

Christian Baues12; Andreas Rosenwald13; Markus Dietlein2;

Peter Borchmann1; Andreas Engert1

1Department I of Internal Medicine, Center for Integrated Oncology Aachen,

Bonn, Cologne, Düsseldorf, Faculty of Medicine and University of Cologne,

German Hodgkin Study Group, Köln, Deutschland

2Department of Nuclear Medicine, Faculty of Medicine and University of

Cologne, Köln, Deutschland

3Inselspital, Universitätsspital Bern, Bern, Schweiz

4Swiss Group for Clinical Cancer Research (SAKK), Bern, Schweiz

5IIIrd Medical Department, Paracelsus Medical University and Salzburg

Cancer Research Institute-CCCIT, Cancer Cluster Salzburg and AGMT

(Arbeitsgemeinschaft Medikamentöse Tumortherapie), Salzburg, Österreich

6Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg,

Deutschland

7Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Deutschland

8Klinikum Bremen-Mitte, Department of Internal Medicine I, Bremen,

Deutschland

9Universitätsklinikum Tübingen, Medizinische Klinik II, Tübingen, Deutschland

10Medizinische Klinik III, Uniklinik Regensburg, Regensburg, Deutschland

11Amsterdam UMC, Dept Hematology, Vrije Universiteit, Cancer Center

Amsterdam, Amsterdam, Niederlande

12Department of Radiooncology and Cyberknife Center, Faculty of Medicine and

University of Cologne, Cologne, Köln, Deutschland

13Institute of Pathology , Julius-Maximilians-Universität Würzburg, Würzburg,

Deutschland

Background: e primary analysis of HD16 revealed that in the treat-

ment of early-stage favorable Hodgkin lymphoma (HL), consolidation

radiotherapy aer chemotherapy cannot be omitted without a clinically

signicant loss of tumor control.

Methods: Between 11/2009 and 12/2015, 1150 patients aged 18-75 years

with newly diagnosed early-stage favorable HL were randomized between

standard combined-modality treatment (CMT) (2xABVD followed by

PET/CT-based staging [PET-2] and 20Gy involved-eld radiotherapy)

and PET-2-guided treatment (omitting radiotherapy aer negative PET-2,

i.e. Deauville score [DS]<3). HD16 aimed at excluding inferiority of PET-

2-guided treatment in terms of a HR≥3.01 for PFS in the PET-2-negative

per-protocol cohort and assessing the prognostic impact of PET-2 among

patients receiving CMT. We now aimed at repeating analyses with longer

follow-up and adding long-term safety data.

Result: Aer a median follow-up of 64 months, PET-2-negative patients

had ve-year PFS rates of 94.2% (95% CI 91.6–96.9) aer CMT (n=328)

and 86.7% (82.5–90.9) aer ABVD alone (n=300; HR=2.05 [1.20-3.51];

p=0.0072). Five-year overall survival was 98.3% (96.9–99.8) and 98.8%

(97.4–100), respectively (p=0.14), with 4/12 documented deaths caused

by second primary malignancies and only 1 by HL. Among patients who

had received CMT, PFS was superior in PET-2-negative (n=353; 5-year

PFS 94.0% [91.4-96.6]) compared with PET-2-positive patients (n=340;

90.3% [86.9-93.6]; p=0.012). e dierence was more pronounced when

the more common cut-o of DS4 was used (DS1-3: n=571; 94.0% [91.9-

96.0] vs. DS≥4: n=122; 83.6% [76.6-90.6]; p<0.0001).

Conclusion: We conclude that radiotherapy cannot be omitted from the

treatment of early-stage favorable HL without a clinically relevant and

statistically signicant loss of ecacy. We could not observe any disad-

vantage of standard CMT over PET-guided therapy in terms of acute or

late toxicities.

Disclosure Statement: e authors declare no conict of interest.

349

Pirtobrutinib; A Next Generation; Highly Selective; Non-covalent

BTK Inhibitor In Previously Treated CLL/SLL: Updated Results

From The Phase 1/2 BRUIN Study

John M. Pagel1; Catherine C. Coombs2; Nirav N. Shah3; Nicole Lamanna4;

Ewa Lech-Maranda5; Toby A. Eyre6; Jennifer A. Woyach7;

William G. Weirda8; Chan Y. Cheah9; Lindsey E. Roeker10; Manish R. Patel11;

Bita Fakhri12; Minal A. Barve13; Constantine Tam14; David Lewis15;

James N. Gerson16; Alvaro J. Alencar17; Paolo Ghia18; Stephen J. Schuster16;

Matthew S. Davids19; Jennifer R. Brown19; Wojciech Jurczak20;

Anthony R. Mato21

1Seattle, Swedish Cancer Institute, Seattle, USA

2Chapel Hill, University of North Carolina at Chapel Hill, Chapel Hill, USA

3Milwaukee, Medical College of Wisconsin, Milwaukee, USA

4New York City, Herbert Irving Comprehensive Cancer Center, Columbia

University, New York City, USA

5Warsaw, Institute of Hematology and Transfusion Medicine, Warsaw, Polen

6Oxford, Oxford University Hospitals NHS Foundation Trust, Churchill Cancer

Center, Oxford, Vereinigtes Königreich

7Columbus, The Ohio State University Comprehensive Cancer Center,

Columbus, USA

8Texas, MD Anderson Cancer Center, Texas, USA

9Perth, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth,

Australien

10New York City, Memorial Sloan Kettering Cancer Center, New York City, USA

11Sarasota, Florida Cancer Specialists/Sarah Cannon Research Institute,

Sarasota, USA

12San Francisco, University of California San Francisco, San Francisco, USA

13Dallas, Mary Crowley Cancer Research, Dallas, USA

14Melbourne, Peter MacCallum Cancer Center, Royal Melbourne Hospital, and

University of Melbourne, Melbourne, Australien

15Plymouth, University Hospitals Plymouth NHS, Plymouth, Vereinigtes

Königreich

16Philadelphia, University of Pennsylvania, Philadelphia, USA

17Miami, University of Miami Miller School of Medicine, Miami, USA

18Mailand, Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele,

Mailand, Italien

19Boston, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA

20Krakow, Maria Sklodowska-Curie National Research Institute of Oncology,

Krakow, Polen

21Memorial Sloan Kettering Cancer Center, New York City, USA

Background: Covalent BTK inhibitors (BTKi) have transformed the man-

agement of chronic lymphocytic leukemia/small lymphocytic lymphoma

(CLL/SLL) although many patients (pts) require additional treatment. In

a phase 1/2 BRUIN study, pirtobrutinib a highly selective, non-covalent

BTKi achieved pharmacokinetic exposures that exceeded its BTK IC96 at

trough, was well tolerated and demonstrated promising ecacy in CLL/

SLL pts despite prior therapy, number of prior lines of therapy, or BTK

C481 mutation status (Mato et al. Lancet 2021;397,10277:892-901).

Methods: BRUIN is a multicenter phase 1/2 study (NCT03740529) of oral

pirtobrutinib monotherapy in pts with advanced B-cell malignancies. e

primary objective for phase 1 was the recommended phase 2 dose (RP2D)

and the primary objective of phase 2 was overall response rate (ORR).

Results: As of 27 September 2020, 323 pts (170 CLL/SLL, 61 MCL, 26

WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT, and 6 other NHL) were treated on

7 dose levels (25-300mg QD). Median age was 69 (range 36-88) years for

CLL/SLL pts. Median number of prior lines of therapy was 3 (range 1-11).

No DLTs were reported, MTD was not reached (n=323) and 200mg QD

was selected as the RP2D. e most frequent treatment-emergent adverse

events regardless of attribution or grade seen in >10% of pts (n=323) were

fatigue (20%), diarrhea (17%) and contusion (13%). e most common

adverse event of grade ≥3 was neutropenia (10%). Five (1%) pts dis-

continued due to treatment-related adverse events. e ORR was 63%

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts168

(95% CI 55-71) among the 139 ecacy evaluable CLL/SLL pts with 69

PRs (50%), 19 PR-Ls (14%), 45 SDs (32%), and 1 PD (1%), and 5 (4%)

discontinued prior to rst response assessment. Median follow up time

was 6 months (range 0.16-17.8+).

Conclusion: Pirtobrutinib was well tolerated and exhibited a wide ther-

apeutic index. Pirtobrutinib demonstrated promising ecacy in heavily

pretreated CLL/SLL pts following multiple prior lines of therapy, includ-

ing a covalent BTKi and a BCL2 inhibitor. Updated data, from ~100 new

pts with CLL and an additional 10 months since the prior data cut will be

presented.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

392

A population based study of treatment of Hodgkin Lymphoma

in older patients with data of the Cancer Registry

of Baden-Württemberg (BW); Germany

Claudia Winzler; Irina Surovtsova; Daria Kokh; Philipp Morakis

Klinische Landesregisterstelle, Krebsregister Baden-Württemberg, Stuttgart,

Deutschland

Introduction: Hodgkin Lymphoma (HL) is a treatable condition with a

5 year survival rate of 80-90%. Older age is an adverse prognostic factor,

which might be related to comorbidities, tumour biology and to therapy

choice. Physicians have to treat a potentially curative lymphoma but pro-

tect their patients from unacceptable toxicities.

Objective: e purpose of the present study was to analyse the primary

treatment of incident classical HL (cHL) in older patients aged > 60 years

compared to younger ones by using data of the Cancer Registry of BW.

Methods: Adult patients with cHL diagnosed between 2016-2020 were

included (approximately 1300 patients; about 25% > 60 years old). Primary

therapy dened as the rst systemic therapy started within 3 months and

radiotherapy within 6 months was compared between patients aged 18-60

years and those aged > 60 years. Chemotherapy regimens were catego-

rized as standard (ABVD and BEACOPP), non-standard, single agent and

no treatment. Dierences in gender, histology, Ann Arbor stage, out-of

hospital therapy and timing of primary therapy were analysed.

Results: e analysis shows that tumours in older patients are more fre-

quently of mixed cellularity and non-specied histology and diagnosed at

a later stage (III or IV). Compared to younger patients, radiotherapy was

less applied. In the elderly, chemotherapy was performed less oen with

standard protocols. BEACOPP is less used compared to young patients.

About 35% of older patients were treated with non-standard protocols.

Among non-standard protocols, AVD, Brentuximab-AVD and PVAG

were most commonly used. e remaining ones were variable other pro-

tocols or single agents.

Conclusions: e data show dierent treatment modalities for patients

with cHL aged > 60 years compared to younger ones. Dierences are

found also for histology and stage. Higher relapse and death rates, as

reported from international studies, might not be due only to age, but also

to tumour biology, tumour extension at diagnosis and therapy modalities.

Disclosure Statement: e authors declare no conict of interest.

411

Characterization of Bruton Tyrosine Kinase Inhibitor

(BTKi)-Related Adverse Events in a Head-to-Head Trial of

Acalabrutinib Versus Ibrutinib in Previously Treated Chronic

Lymphocytic Leukemia (CLL)

Stephan Stilgenbauer1; John F. Seymour2; John C. Byrd3; Peter Hillmen4;

Paolo Ghia5; Arnon P. Kater6; Asher Chanan-Khan7; Richard R. Furman8;

Susan O’brien9; Jennifer R. Brown10; Anthony Mato11;

Nataliya Kuptsova-Clarkson12; Paulo Miranda12; Dennis Wagner13;

Kara Higgins14; Sophia Sohoni14; Wojciech Jurczak15

1University of Ulm, Internal Medicine III, Ulm, Deutschland

2Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of

Melbourne, Victoria, Australien

3The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

4St. James’s University Hospital, Leeds, Vereinigtes Königreich

5Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,

Italien

6Amsterdam University Medical Center, Amsterdam, on behalf of Hovon,

Niederlande

7Mayo Clinic Jacksonville, Jacksonville, FL, USA

8Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA

9Chao Family Comprehensive Cancer Center, University of California-Irvine,

Irvine, CA, USA

10Dana-Farber Cancer Institute, Boston, MA, USA

11University of Pennsylvania, Philadelphia, PA, USA

12AstraZeneca, Gaithersburg, MD, USA

13AstraZeneca, Mississauga, Ontario, Kanada

14AstraZeneca, South San Francisco, CA, USA

15Maria Sklodowska-Curie National Research Institute of Oncology, Krakow,

Polen

Background: As submitted to ASH 2021, we report additional data

of a phase 3 head-to-head trial of acalabrutinib (A) vs ibrutinib (Ibr)

(NCT02477696) to further characterize BTKi-related adverse events

(AEs) and the safety prole of A and Ibr.

Methods: Patients (Pt) received oral A BID or Ibr QD until disease pro-

gression or unacceptable toxicity. Overall incidence, exposure-adjusted

(exp-adj) incidence, and exp-adj time with event were assessed for the

most common BTKi-related AEs. Atrial brillation (ab)/utter, hyper-

tension, and bleeding events were further characterized by time to onset,

cumulative incidence, Pt subgroup, and AE management.

Result: A total of 533 Pt (A, n=268; Ibr, n=265) were randomized; median

treatment exposures were 38.3 and 35.5 months (mo), respectively.

Among events of clinical interest, incidences of any-grade ab/utter,

hypertension, bleeding, diarrhea, arthralgia, contusion, urinary tract

infection (UTI), back pain, muscle spasms and dyspepsia were statisti-

cally higher with Ibr with higher exp-adj incidence and exp-adj time with

event (except for UTI). Incidences and exp-adj time with event of head-

ache and cough were statistically higher with A. Total exp-adj time with

event for all any-grade AEs was 37% higher with Ibr. Any-grade ab/ut-

ter, hypertension and bleeding events showed lower cumulative incidence

with A at 6, 12, 18 and 24 mo, and occurred less frequently in subgroups

of age and prior line of therapy. Among Pt without prior history, any grade

ab/utter and hypertension occurred less frequently and showed a 63%

and 77% reduction rate favoring A, respectively. Among all Pt, concom-

itant medication use for ab/utter was less common for A (8%) vs Ibr

(14%), with antithrombotic use reported in 5% vs 9% of Pt, respectively.

Concomitant medication use for hypertension was less common for A

(5%) vs Ibr (19%).

Discussion and Conclusion: In this head-to-head trial of BTKis in CLL,

event-based analyses demonstrated a higher BTKi-related toxicity bur-

den with Ibr, with a lower impact of CV-related toxicity with A across

subgroups.

Sponsor: Acerta Pharma BV; AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 169

414

Acalabrutinib vs Rituximab Plus Idelalisib or Bendamustine in

Relapsed/Refractory Chronic Lymphocytic Leukemia: ASCEND

Results at ~4 Years of Follow-up

Manfred Welslau1; Wojciech Jurczak2; Andrzej Pluta3; Malgorzata Wach4;

Daniel Lysak5; Martin Šimkovič6; Irina Kryachok7; Arpad Illes8; Javier De la

Serna9; Sean Dolan10; Philip Campbell11; Gerardo Musuraca12; Abraham

Jacob13; Eric Avery14; Jae Hoon Lee15; Ganna Usenko16; Min Hui Wang17;

Ting Yu17; Paolo Ghia18

1MVZ am Klinikum Aschaenburg, Aschaenburg, Deutschland

2Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Polen

3Department of Hematological Oncology, Oncology Specialist Hospital,

Brzozow, Polen

4Department of Hemato-Oncology and Bone Marrow Transplantation, Medical

University of Lublin, Lublin, Polen

5Fakultní Nemocnice Plzen, Pilsen, Tschechische Republik

6University Hospital Hradec Kralove, Charles University, Hradec Kralove,

Tschechische Republik

7National Cancer Institute, Kiev, Ukraine

8University of Debrecen, Debrecen, Ungarn

9Hospital Universitario 12 de Octubre, Madrid, Spanien

10Saint John Regional Hospital, University of New Brunswick, New Brunswick,

Kanada

11Barwon Health, University Hospital Geelong, Geelong, Victoria, Australien

12Istituto Scientico Romagnolo per lo Studio e la Cura dei Tumori, Meldola,

Italien

13Royal Wolverhampton Hospital National Health Service Trust, Wolverhampton,

Vereinigtes Königreich

14Nebraska Hematology Oncology, Lincoln, NE, USA

15Gachon University Gil Medical Center, Incheon, Republik Korea

16City Clinical Hospital, No. 4 DCC, Dnipro, Ukraine

17AstraZeneca, South San Francisco, CA, USA

18Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,

Italien

Background: In primary analysis of ASCEND (median follow-up 16.1

months (mo)), acalabrutinib (A) showed superior ecacy with acceptable

tolerability prole vs idelalisib (Id) + rituximab (R) (IdR) or bendamus-

tine (B) + R (BR) in pt with relapsed/refractory (R/R) chronic lympho-

cytic leukemia (CLL).1 We report the results at ~4 years (y) of follow-up

which were rst submitted to ASCO 2022.

Methods: In this multicenter, open-label phase 3 study (NCT02970318),

pt with R/R CLL received A until progression or unacceptable toxicity or

investigator’s (INV) choice of IdR (Id: until progression or unacceptable

toxicity; R: 8 infusions) or BR (6 cycles). Crossover to A was permitted

in pt who progressed on IdR/BR. Progression-free survival (PFS), overall

survival (OS), overall response rate (ORR), and safety were assessed.

Result: 310 pt (A, n=155; IdR, n=119; BR, n=36) were randomized

(median age 67 y; del(17p) 15%, unmutated IGHV 74%, Rai stage 3/4

42%). At median follow-up of 46.5 mo (A) and 45.3 mo (IdR/BR), A sig-

nicantly prolonged INV-assessed PFS vs IdR/BR (median not reached

(NR) vs 16.8 mo; P<0.0001); 42-mo PFS rates were 62% for A vs 19% for

IdR/BR. In pt with del(17p), median PFS was NR (A) vs 13.8 mo (IdR/

BR; P<0.0001). In pt with unmutated IGHV, median PFS was NR (A) vs

16.2 mo (IdR/BR; P<0.0001). Median OS was NR in both arms; 42-mo

OS rates were 78% (A) vs 65% (IdR/BR). ORR was 83% (A) vs 84% (IdR/

BR) (ORR + partial response with lymphocytosis: 92% (A) vs 88% (IdR/

BR)). Adverse Events led to drug discontinuation in 23% of A, 67% of

IdR, and 17% of BR pt. Events of clinical interest (A vs IdR/BR) included

all-grade atrial brillation/utter (8% vs 3%), all-grade hypertension (8%

vs 5%), all-grade major hemorrhage (3% vs 3%), and grade ≥3 infections

(29% vs 29%).

Discussion and Conclusion: At ~4 y of follow-up, A maintained ecacy

compared with standard-of-care regimens and a consistent tolerability

prole in R/R CLL.

Indication of source:

1 Ghia et al. J Clin Oncol. 2020;38:2849-2861

Sponsor: Acerta Pharma BV; AstraZeneca

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

516

Pirtobrutinib, A Next Generation, Highly Selective,

Non-covalent BTK Inhibitor In Previously Treated Mantle Cell

Lymphoma: Updated Results From The Phase 1/2 BRUIN Study

Nirav N. Shah1; Alvaro J. Alencar2; James N. Gerson3; Manish R. Patel4;

Bita Fakhri5; Wojciech Jurczak6; Xuan Tan7; Katharine Lewis7;

Timothy Fenske1; Catherine C. Coombs8; Ian Flinn9; David Lewis10;

Steven Le Gouill11; M. Lia Palomba12; Jennifer Woyach13; John M. Pagel14;

Nicole Lamanna15; Johnathon B. Cohen16; Minal A. Barve17; Paolo Ghia18;

Toby A. Eyre19; Anthony R. Mato12; Chan Y. Cheah7; Michael L. Wang20

1Milwaukee, Medical College of Wisconsin, Milwaukee, USA

2Miami, Sylvester Comprehensive Cancer Center, Miami, USA

3Philadelphia, University of Pennsylvania, Philadelphia, USA

4Sarasota, Florida Cancer Specialists/Sarah Cannon Research Institute,

Sarasota,USA

5San Francisco, University of California San Francisco, San Francisco, USA

6Krakow, Maria Sklodowska-Curie National Research Institute of Oncology,

Krakow, Polen

7Perth, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth,

Australien

8Chapel Hill, University of North Carolina at Chapel Hill, Chapel Hill, USA

9Nashville, Sarah Cannon Research Institute, Nashville, USA

10Plymouth, University Hospitals Plymouth NHS, Plymouth, Vereinigtes

Königreich

11Nantes, Service d’hématologie clinique du CHU de Nantes, INSERM CRCINA

Nantes-Angers, NeXT Université de Nantes, Nantes, Frankreich

12New York City, Memorial Sloan Kettering Cancer Center, New York City, USA

13Columbus, The Ohio State University Comprehensive Cancer Center,

Columbus, USA

14Seattle, Swedish Cancer Institute, Seattle, USA

15New York City, Herbert Irving Comprehensive Cancer Center, Columbia

University, New York City, USA

16Atlanta, Winship Cancer Institute, Emory University, Atlanta, USA

17Dallas, Mary Crowley Cancer Research, Dallas, USA

18Mailand, Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele,

Mailand, Italien

19Oxford, Oxford University Hospitals NHS Foundation Trust, Churchill Cancer

Center, Oxford, Vereinigtes Königreich

20Texas, MD Anderson Cancer Center, Texas, USA

Background: Covalent BTK inhibitors (BTKi) have transformed the man-

agement of mantle cell lymphoma (MCL) although a majority of patients

(pts) on these agents require additional treatment. In a phase 1/2 BRUIN

study, pirtobrutinib a highly selective, non-covalent BTKi achieved phar-

macokinetic exposures that exceeded its BTK IC96 at trough, was well

tolerated and demonstrated promising ecacy in heavily pretreated,

poor-prognosis MCL pts, most of whom had prior treatment with a cova-

lent BTKi (Mato et al. Lancet 2021;397, 10277:892-901).

Methods: BRUIN is a multicenter phase 1/2 study (NCT03740529) of oral

pirtobrutinib monotherapy in pts with advanced B-cell malignancies. e

primary objective for phase 1 was to determine the recommended phase

2 dose (RP2D) and the primary objective of phase 2 was overall response

rate (ORR).

Results: As of 27 September 2020, 323 pts (170 CLL/SLL, 61 MCL, 26

WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT, and 6 other NHL) were treated

on 7 dose levels (25-300mg QD).Median age was 69 (range 50-87) years

for MCL pts. Among the 61 MCL pts, median number of prior lines of

therapy was 3 (range, 1-8). No DLTs were reported and MTD was not

reached (n=323) and 200mg QD was selected as the RP2D. e most

frequent treatment-emergent adverse events regardless of attribution or

grade seen in >10% of pts (n=323) were fatigue (20%), diarrhea (17%)

and contusion (13%). e most common adverse event of grade ≥3 was

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts170

neutropenia (10%). At the ecacy cuto date, 52 prior BTKi treated MCL

pts were ecacy evaluable with an ORR of 52% (95% CI 38-66) with 13

CR (25%), 14 PR (27%), 9 SD (17%), 11 PD (21%), and 5 (10%) discontin-

uations prior to rst response assessment. Median follow up was 6 months

(range 0.7-18.3+).

Conclusion: Pirtobrutinib was well tolerated and exhibited a wide ther-

apeutic index. Pirtobrutinib demonstrated promising ecacy in heavily

pretreated, poor-prognosis MCL following multiple prior lines of therapy,

including a covalent BTKi. Updated data from ~60 new pts with MCL and

an additional 10 months since the prior data cut will be presented.

Disclosure Statement: e authors declare no conict of interest.

534

Iberdomide (IBER) in combination with dexamethasone (DEX)

and daratumumab (DARA), bortezomib (BORT), or carlzomib

(CFZ) in patients (pts) with relapsed/refractory multiple

myeloma (RRMM)

Stefan Knop1; Sagar Lonial2; Paul Richardson3; Rakesh Popat4;

Edward A. Stadtmauer5; Jeremy T. Larsen6; Albert Oriol7; Sundar

Jagannath8; Gordon Cook9; Ashraf Z. Badros10; Paula Rodriguez-Otero11;

David Siegel12; Tuong VI Nguyen13; Antonia DI Micco14; Alpesh Amin13;

Min Chen13; Elisabeth Kueenburg14; Niels W.C.J. van de Donk15

1Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg,

Deutschland

2Winship Cancer Institute, Emory University, Atlanta, GA, USA

3Dana-Farber Cancer Institute, Boston, MA, USA

4NIHR UCLH Clinical Research Facility, University College London Hospitals NHS

Foundation Trust, London, Vereinigtes Königreich

5University of Pennsylvania, Philadelphia, PA, USA

6Mayo Clinic, Scottsdale, AZ, USA

7Institut de Recerca contra la Leucèmia Josep Carreras and Institut Català

d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spanien

8The Mount Sinai Hospital, New York, NY, USA

9Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University

of Leeds, Leeds, Vereinigtes Königreich

10The University of Maryland Marlene and Stewart Greenebaum Comprehensive

Cancer Center, University of Maryland Medical Center, Baltimore, MD, USA

11Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spanien

12Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack

University Medical Center, Hackensack, NJ, USA

13Bristol Myers Squibb, Princeton, NJ, USA

14Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Schweiz

15Amsterdam University Medical Center, VU Amsterdam, Department of

Hematology, Cancer Center Amsterdam, Amsterdam, Niederlande

Background: Here we report results from CC-220-MM-001

(NCT02773030), an ongoing phase 1/2 study evaluating MTD/RP2D,

safety, and ecacy of IBER+DARA+DEX (IberDd), IBER+BORT+DEX

(IberVd), and IBER+CFZ+DEX (IberKd) in pts with RRMM.

Methods: Eligible pts received ≥ 2 (IberDd and IberKd cohorts) or ≥ 1

prior regimens (IberVd cohort), containing LEN/POM, and a PI. All pts

had progressed ≤ 60 days of last therapy. Escalating oral doses of IBER

were given day (D)1–21 of each 28-d cycle in the IberDd and IberKd

cohorts, D1–14 of each 21-D cycle in the IberVd cohort.

Result: As of April 8, 2021, 43 pts had received IberDd, 25 IberVd, and 9

IberKd. Median age was 67, 64, and 61 y, and median time since diagno-

sis was 7.35, 7.10, and 6.70 y in the IberDd, IberVd, and IberKd cohorts,

respectively. Exposure to prior regimens was heterogeneous and ≥ 33% pts

in the 3 cohorts were triple-class refractory. IBER doses ranged from 1.0 to

1.6 mg. Median follow-up was 4.17, 4.86, and 5.03 mo, 22 (51%), 6 (24%),

and 5 (56%) pts continue on treatment, and median cycles received were

4, 6, and 5 with IberDd, IberVd, and IberKd, respectively. Hematologic

grade 3‒4 TEAEs of interest included neutropenia (67%), leukopenia

(23%), anemia (21%), and febrile neutropenia (5%) with IberDd; neutro-

penia (28%) and thrombocytopenia (24%) with IberVd; and lymphope-

nia (44%) and neutropenia (33%) with IberKd. e ORR was 46% with

IberDd, 56% with IberVd, and 50% with IberKd. Median time to response

was 4.1 (4.0‒12.0), 3.6 (3.0‒13.1), and 4.1 (4.1‒8.1) wk in the IberDd,

IberVd, and IberKd cohorts, respectively. Median duration of response is

35.7 wk in the IberVd cohort (not reached in the other cohorts). RP2D

was determined at 1.6 mg in the IberDd cohort; dose evaluation continues

in the other cohorts.

Discussion: ese results support further development of IBER-based

regimens in MM, including initiation of phase 3 combination studies.

Conclusion: In pts with heavily pretreated RRMM, IberDd, IberVd,

and IberKd showed a manageable safety prole and promising ecacy.

Previously published in Lonial S, et al. HemaSphere 2021;5(S2):49.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

574

Response to vaccination against Covid-19-virus in patients

with hematologic malignancies with respect to diagnosis and

treatment

Christoph Losem1; Lars Galonska2; Eike Albers3

1TZN Tumorzentrum Niederrhein GmbH, Neuss, Deutschland

2MVZ Hämatologie - Onkologie im Rhein-Kreis, Neuss, Deutschland

3Labor Quade & Kollegen GmbH, Köln, Deutschland

Background: In patients with hematologic malignancies response to

Covid-19-vaccination is unpredictable because these patients were

excluded from clinical trials in the past.

Methods: We measured B-cell-response by means of Covid-S1-antibody

reaction (SARS-CoV-2 IgG, Siemens Atellica IM) at earliest 3 weeks aer

second vaccination with the BNT162b2. In some patients T-cell-response

is determined by a Covid-Quantiferon-test (QuantiFERON SARS-CoV-2,

Qiagen)

Result: Untill August 2021 results for Covid-S1-antibody-testing were

present in 89 patients. In 46 of these patients response to vaccination was

missing by means of antibody determination (no measurable antibodies

against S1-antigen). Patients with no response to vaccination were mainly

patients with B-cell-lymphoma but also patients with multiple myeloma

und chronic myelomonocytic leukemia. 56 of 89 patients were on or aer

therapy with CD20-antibodies, respectivley. 39 of these 56 Patients had no

response to vaccination.

Discussion: Most available data concerning response to vaccination

against Covid-19-virus in patients with hematologic malignancies relate

to chronic B-cell leukemia and Covid-S1-antibody response. We present

single institution data of a variety of malignant hematologic diseases and

evalutate T-cell-response additionally.

Conclusion: Patients with hematologic malignancies and treatment with

CD20-abtibodies have a very high risk not to respond to vaccination

against Covid-19-virus. Since vaccination and testing has not nished yet

in our patients we will present updated results on response to vaccination

with respect to hematologic diagnosis, total dose of and intervall to CD20-

antibody-therapy on DKK-meeting in 2022.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 171

638

The eects of switching anti-CD20 antibodies on treatment

response and outcome for patients with B-Non-Hodgkin

lymphomas: A single-center retrospective data analysis

Constantin Bartzke; Claudia Baldus; Christiane Pott

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin

II mit den Schwerpunkten Hämatologie und Onkologie, Kiel, Deutschland

Background: With the approval of rituximab biosimilars, a switch from

rituximab to anti-CD20 biosimilar can occur during treatment of B-cell

lymphomas (B-NHL). Only few data report whether an antibody switch

impacts on treatment response and prognosis. In this retrospective obser-

vational study, we aimed to evaluate response and outcome in B-NHL

aer switching from reference rituximab to a biosimilar.

Methods: B-NHL patients (pts.) who received an anti-CD20 antibody

treatment (January 2017 - December 2018) were evaluated regarding treat-

ment response to immunochemotherapy including rituximab (Mabthera)

followed by a biosimilar (Rixathon) as rst-line or salvage therapy. Data

were extracted from the electronic patient record, anonymized and evalu-

ated including response to treatment, progression-free survival (PFS) and

overall survival (OS).

Results: In 211 pts. (median age 69 years) the most common histological

subgroups was diuse large B-cell lymphoma (DLBCL) (38.4%), follicu-

lar lymphoma (FL) (26.5%), marginal zone lymphoma (11,8%) and other

subtypes (23,2%).171 pts. received a rst-line therapy, 1355 anti-CD20

antibody doses were applied during induction treatment (n=1051) and

maintenance (n=304). Anti-CD20 treatment consisted of 48.2% Mabthera,

34.8% Rixathon, 9.2% Mabthera s.c. 7.8% Obinutuzumab. A switch was

done in 51 rst-line treatments (24 DLBCL, 12 FL ,15 other subtypes).

Response to induction treatment was similar in switch and non-switch

groups in all histologic subtypes. Median PFS and OS was not reached

at a median follow up of 23 months and was comparable among switch

and non-switch groups. Similarly, in pts. receiving second-line treatment

(n=43) (switch in 7 pts.) no dierences in overall response, PFS and OS

occured (median follow up 26 months).

Discussion: e results suggest that a switch of Mabthera to the biosimi-

lar Rixathon has no impact on the eectiveness and outcome in dierent

subgroups of B-NHL.

Conclusion: A switch of Mabthera to the biosimilar Rixathon leads to

comparable outcomes and can be done safely in clinical routine.

Disclosure Statement: e authors declare no conict of interest.

679

Clinical characteristics and outcome of patients with relapsed

DLBCL undergoing autologous SCT, allogeneic SCT and CAR-T

cell therapy

Amelie Isabel Hartmann; Natalie Schub; Marianne Helweg;

Christiane Pott; Claudia Baldus

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin

II mit den Schwerpunkten Hämatologie und Onkologie, Kiel, Deutschland

Background: Patients (pts) with diuse large B-cell lymphoma (DLBCL)

at rst chemo-sensitive relapse receive high-dose chemotherapy followed

by autologous stem cell transplantation (ASCT). At 2nd relapse, allogeneic

SCT (alloSCT) or CAR-T cell therapy (CART) have a curative potential.

Methods: is is a retrospective analysis of 126 pts with DLBCL who

underwent ASCT in rst (n=69) or 2nd relapse (n=16), alloSCT (n=23) or

CART (n=18) in 2nd relapse at UKSH Kiel from 2004 to April 2021

Result: Median age was 61 years in CART pts, 50 y in alloSCT and 61 y

in ASCT pts at 2nd relapse. CART pts presented with higher ECOG score

(28% ECOG 2-3) compared to alloSCT and ASCT pts (4% and 25%,

respectively) and higher HCT-CI score (2,44) (1,3 and 2,2 respectively).

Response to salvage treatment (complete or partial remission) was less

frequently achieved prior to CART (39%) than to alloSCT (70%) and

ASCT at 2nd relapse (44%). 56% of CART pts had chemorefractory disease,

while this was the case in only 22% alloSCT and 44% ASCT pts. Median

number of prior treatments was 2,5 for CART, 3 for alloSCT, and 3,25 for

ASCT pts. Response to treatment at 3 months was 50% aer CART, 65%

aer alloSCT and only 25% aer ASCT in 2nd relapse. At 6 months, 22% of

CART pts were still in remission compared to 35% aer alloSCT and 25%

aer ASCT. Early death during the rst 6 months aer treatment occurred

most frequently aer ASCT in 2nd relapse (38%) with 5 pts succumbing to

progressive disease (PD) and 1 due to an unrelated cause. 6% of CART pts

and 13% aer alloSCT died from PD and further 6% of CART pts and 13%

aer alloSCT from treatment related cause.

Discussion: Patients receiving CART were older and in worse condition

than those receiving ASCT or alloSCT. ASCT at 2nd relapse does not suf-

ciently control aggressive DLBCL leading to early death. AlloSCT is an

eective but toxic approach for a selected patient population.

Conclusion: CAR-T cell therapy at 2nd relapse is a useful treatment option

also for patients not qualifying for a more intensive treatment but patient

selection criteria need to be dened to improve long-term outcome.

Disclosure Statement: e authors declare no conict of interest.

691

A meta-analysis of ecacy of pomalidomide-based regimens

for the treatment of relapsed or refractory multiple myeloma

(RRMM) after lenalidomide (LEN) exposure

Katja Weisel1; Faith E. Davies2; Xavier Leleu3; Prisca Vogel4;

Sujith Dhanasiri5; Pauline Le Nouveau6

1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

2New York University Grossman School of Medicine, Clinical Myeloma Program

Perlmutter Cancer Center, New York, USA

3Service d’Hématologie et Thérapie Cellulaire, Hôpital La Milétrie, Poitiers,

Frankreich

4Celgene, a Bristol Myers Squibb Company, Boudry, Schweiz

5Bristol Myers Squibb, Princeton, USA

6Amaris Consulting, Levallois-Perret, Frankreich

Background: Pomalidomide (POM)-based combination(s) are a standard

therapy for patients (pts) with RRMM previously treated with LEN. e

aim of this work was to provide a meta-analysis of progression-free sur-

vival (PFS) outcomes reported for POM-based combinations and generate

a pooled ecacy estimate.

Methods: A targeted literature search was performed to identify studies

conducted 2016–2020 in pts with RRMM previously treated with LEN.

Studies included in the meta-analysis enrolled pts who were treated

with POM plus dexamethasone (Pd) in combination with a proteasome

inhibitor (bortezomib [PVd], carlzomib [KPd], or ixazomib [IxaPd]),

monoclonal antibody (elotuzumab [EloPd], daratumumab [DPd], or

isatuximab [IsaPd]), or an alkylating agent (cyclophosphamide [PCd]).

Published Kaplan–Meier curves were digitized to reconstruct individual

patient data (IPD) through the Guyot algorithm. Reconstructed IPD were

used to conduct 3 unadjusted meta-analyses that generated the median

PFS for 3 groups: pts from studies with second-line (2L) treatment only,

pts from studies that included 2L pts (2L+), and all pts from all studies.

Result: Six randomized controlled trials (OPTIMISMM – PVd vs Vd,

APOLLO – DPd vs Pd, EMN-011 – KPd, ELOQUENT-3 – EloPd vs

Pd, ICARIA-MM – IsaPd vs Pd, NCT01432600 – PCd vs Pd) and 6 sin-

gle-arm trials (MM-014 – DPd, MMRC – KPd, NCT02185820 – KPd,

NCT02119468 – IxaPd, NCT02176213 – PCd, IFM2013 – PCd) were

identied. Median PFS was 21.3 months for 2L only pts, 16.9 months for

2L+ pts, and 14.1 months for all pts.

Discussion: POM-based combinations are an eective treatment strategy

in pts with RRMM previously treated with LEN. is analysis found that

POM-based regimens were more eective in pts in early-line treatment

(2L) compared with the overall population. POM delivers consistent e-

cacy and synergy in combination with proteasome inhibitors and mono-

clonal antibodies.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts172

Conclusion: ese data suggest that class switch is not always necessary

when making treatment decisions for pts with RRMM.

Reference:

Davies FE, et al. HemaSphere 2021;5:e478–479. EP1013.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

709

Idecabtagene vicleucel (ide-cel; bb2121); a BCMA-directed

CAR T cell therapy; for the treatment of patients with relapsed

and refractory multiple myeloma (RRMM): updated results

from KarMMa

Hermann Einsele1; Larry D. Anderson Jr2; Nina Shah3; Sundar Jagannath4;

Jesús Berdeja5; Sagar Lonial6; Noopur Raje7; David S. Siegel8;

Yi Lin9; Philippe Moreau10; Ibrahim Yakoub-Agha11; Michel Delforge12;

Hartmut Goldschmidt13; Katja Weisel14; Michele Cavo15; Donna Reece16;

Alessandro Rambaldi17; Anna Truppel-Hartmann18; Payal Patel19;

Liping Huang19; Timothy B. Campbell19; Kristen Hege19; Jesús San-Miguel20;

Nikhil C. Munshi21; Albert Oriol22

1University Hospital Würzburg, Würzburg, Deutschland

2Simmons Comprehensive Cancer Center, UT Southwestern Medical Center,

Dallas, USA

3University of California San Francisco, San Francisco, USA

4Mount Sinai Hospital, New York, USA

5Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA

6Emory School of Medicine, Atlanta, USA

7Massachusetts General Hospital, Boston, USA

8Hackensack University Medical Center, Hackensack, USA

9Mayo Clinic, Rochester, USA

10Centre Hospitalier Universitaire de Nantes, Nantes, Frankreich

11CHU de Lille, Univ Lille, INSERM U1286, Innite, Lille, Frankreich

12University Hospital Leuven, Leuven, Belgien

13University Hospital Heidelberg, Heidelberg, Deutschland

14University Medical Center of Hamburg-Eppendorf, Hamburg, Deutschland

15Bologna University School of Medicine, Bologna, Italien

16Princess Margaret Cancer Centre, Toronto, Kanada

17University of Milan and ASST Papa Giovanni XXII, Bergamo, Italien

18bluebird bio, Cambridge, USA

19Bristol Myers Squibb, Princeton, USA

20Clínica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spanien

21The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple

Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston,

USA

22Institut Josep Carreras and Institut Català d’Oncologia, Hospital Germans Trias i

Pujol, Badalona, Spanien

Background: Patients (pts) with RRMM previously treated with immuno-

modulatory agents (IMiDs), proteasome inhibitors (PIs), and anti-CD38

monoclonal antibodies (mAbs) have poor outcomes with subsequent

therapy (tx). Ide-cel, a BCMA-directed CAR T cell tx, showed frequent,

deep, and durable responses in heavily pretreated pts with RRMM in the

pivotal KarMMa study (NCT03361748; Munshi NC et al. N Engl J Med

2021). We report updated results from this trial.

Methods: Pts had ≥ 3 prior regimens (including IMiD, PI, and anti-CD38

mAb) and disease refractory to last tx per IMWG criteria. Aer 3 days of

lymphodepletion, pts received 150–450 × 106 CAR+ T cells (target dose

levels). Endpoints included overall response rate (ORR; primary), com-

plete response (CR) rate (key secondary), progression-free survival (PFS),

overall survival (OS), and safety.

Result: Of 140 enrolled pts, 128 received ide-cel. Among treated pts,

median age was 61 y. Pts had a median of 6 prior tx, with 84% being

triple-class refractory and 26% penta-refractory (2 IMiDs, 2 PIs, and 1

anti-CD38 mAb). Most pts (88%) had bridging therapy. At data cuto

(Dec 21, 2020), median follow-up for surviving pts was 24.8 mo. ORR was

73% (CR rate, 33%); median PFS was 8.6 mo. In pts with ≥ CR, median

PFS was 22.4 mo. Outcomes improved at higher doses, with ORR of 81%,

CR rate of 39%, and median PFS of 12.2 mo at 450 × 106 CAR+ T cells.

Median OS in all treated pts was 24.8 mo; the 24-mo OS rate was 51%.

Most common any-grade toxicities were neutropenia (91%) and cytokine

release syndrome (CRS; 84%). CRS was mostly grade 1/2; 5 pts (4%) had

grade 3; 1 pt each (< 1%) had grade 4 and 5 events. Investigator-identied

neurotoxicity occurred in 23 pts (18%); 5 (4%) had grade 3 and 0 had

grade ≥ 4 events.

Discussion: Updated results from KarMMa continue to demonstrate

durable and deep responses with ide-cel in triple-class–exposed pts with

RRMM.

Conclusion: Ecacy and safety data reect prior reports and support a

favorable clinical benet–risk prole for ide-cel across target dose levels.

Prior presentation

IMW 2021. Abstract OAB27.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

957

Accuracy and Reliability of German Websites for Information

on Monoclonal Gammopathy of Undetermined Signicance

Emma Kreutzer1; Henrike Staemmler1; Sandra Sauer2; Katharina

Kriegsmann2

1Universitätsklinikum Heidelberg - Medizinische Fakultät, Heidelberg,

Deutschland

2Universitätsklinikum Heidelberg, Heidelberg, Deutschland

Background: Monoclonal gammopathy of undetermined signicance

(MGUS) is a clonal, premalignant plasma cell or B-cell disorder. MGUS

patients oen seek disease-related information online. However, the qual-

ity of online resources available for MGUS is questionable.

Methods: e quality of 900 German websites from Google, Bing, and

Yahoo was evaluated.

Result: e websites did not dier regarding their search rank or between

the search engines. e 83 unique websites showed a medium to poor

general quality (median JAMA score 3 of maximum 4 points, only 4%

websites with a valid HON certicate). e patient- (user-) focused qual-

ity was poor (median sum DISCERN score 24 of maximum 80 points).

e reading level was very dicult (29 of maximum 100 points according

to the Flesch Reading Ease score). e content level was very low (11 of

maximum 50 points). 23% of websites contained misleading/wrong facts.

Websites provided by scientic/governmental organizations had a higher

content level compared to websites provided by foundation/advocacy or

news/media.

Discussion: Similar previously published analyses oen focus on oto-

rhinolaryngology-related topics, idiopathic pulmonary brosis, SARS-

CoV-2 or neurological disorders. Precancerous conditions and cancer

entities were rarely in the focus of such evaluations. is study was per-

formed in a reproducible and objective score-based manner, applying a set

of well-established scores covering the aspects of general, patient- (user-)

focused quality, and MGUS-related content.

Conclusion: MGUS-relevant online sources showed low general and

patient-focused quality and poor content. Information is provided on a

high reading level. Incorporation of quality indices and regular review of

content is warranted.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 173

971

ELOQUENT-3 Trial: Elotuzumab Plus Pomalidomide and

Dexamethasone for Relapsed/Refractory Multiple Myeloma -

Final Overall Survival Analysis

Marc-Steen Raab1; Meletios Dimopoulos2; Dominik Dytfeld3; Sebastian

Grosicki4; Philippe Moreau5; Naoki Takezako6; Mitsuo Hori7; Xavier Leleu8;

Richard Leblanc9; Kenshi Suzuki10; Paul G Richardson11; Mihaela Popa

Mckiver12; Ying-Ming Jou12; David Yao12; Prianka Das12; Jesús San-Miguel13

1Heidelberg University Hospital, Department of Medicine V, Heidelberg,

Deutschland

2National and Kapodistrian University of Athens School of Medicine, Athens,

Griechenland

3Karol Marcinkowski University of Medical Sciences, Department of Hematology

and Bone Marrow Transplantation, Poznań, Polen

4Silesian Medical University, Katowice, Polen

5University Hospital, Nantes, Frankreich

6National Hospital Organization Disaster Medical Center, Department of

Hematology, Tokyo, Japan

7Ibaraki Prefectural Central Hospital, Department of Hematology, Kasama, Japan

8Centre Hospitalier Universitaire de Poitiers–La Milétrie, Poitiers, Frankreich

9University of Montreal, Hôpital Maisonneuve-Rosemont, Montreal, Kanada

10Japanese Red Cross Medical Center, Department of Hematology, Tokyo, Japan

11Dana–Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center,

Boston, USA

12Bristol Myers Squibb, Princeton, USA

13Clínica Universidad de Navarra (CUUN), Centro de Investigación Médica

Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Centro de

Investigación Biomédica en Red de Cáncer (CIBERONC), Pamplona, Spanien

Background: In the randomized phase 2 ELOQUENT-3 trial

(NCT02654132), elotuzumab combined with pomalidomide/dexameth-

asone (EPd) signicantly improved progression-free survival (PFS) ver-

sus pomalidomide/dexamethasone (Pd) in patients (pts) with relapsed/

refractory multiple myeloma (RRMM). A preliminary analysis of overall

survival (OS) (minimum follow-up of 9.1 months [mo]) showed a trend

favoring EPd over Pd (hazard ratio [HR] 0.62; 95% CI, 0.30–1.28). Here

we present nal OS results.

Methods: Pts with RRMM who had received ≥ 2 prior lines of therapy,

disease refractory to last therapy, and either refractory or relapsed and

refractory to lenalidomide and a proteasome inhibitor (PI), were random-

ized (1:1) to receive EPd or Pd. e primary endpoint was PFS per inves-

tigator assessment. OS was a secondary endpoint planned to be tested

hierarchically. Final OS analysis was pre-specied to occur aer 78 deaths

and was also analyzed within pt subgroups.

Result: A total of 117 pts were randomized to EPd (n = 60) and Pd (n

= 57). At the January 11, 2021 data cuto (minimum follow-up of 45

mo), among treated pts (EPd, 60; Pd, 55), there were 37 (61.7%) deaths

in the EPd group and 41 (74.5%) in the Pd group, most commonly due

to disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was

signicantly improved with EPd (29.8 [22.9–45.7] mo) versus Pd (17.4

[13.8–27.7] mo), with a HR of 0.59 (95% CI, 0.37–0.93; P = 0.0217). EPd

improved OS in most pt subgroups. e safety prole of EPd was consis-

tent with prior reports, with no new safety signals detected.

Discussion: EPd demonstrated a statistically signicant and clinically

meaningful improvement in OS versus Pd in pts with RRMM previously

treated with lenalidomide and a PI who had disease refractory to last

therapy.

Conclusion: In this setting, ELOQUENT-3 is the rst randomized study

of a triplet regimen incorporating a monoclonal antibody and Pd that

improved both PFS and OS signicantly.

ese data were presented previously (Dimopoulos MA, et al. 18th

International Myeloma Workshop; September 8–11, 2021; Vienna,

Austria. Poster P-193).

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

991

Exploring Alternative Dosing Regimens of Single-Agent

Belantamab Mafodotin on Safety and Ecacy in Patients

With Relapsed or Refractory Multiple Myeloma (RRMM):

DREAMM-14

Hans Salwender1; Malin Hultcrantz2; Dave Kleinman3;

Pavandeep Ghataorhe4; Astrid Mckeown4; Wei He4; Thomas Ling4;

Roxanne Jewell4; Julie Byrne4; Laurie Eliason4; Emma Scott4;

Joanna Opalinska4

1Askepios Tumorzentrum Hamburg, AK Altona and St. Georg, Hamburg,

Germany

2Memorial Sloan Kettering Cancer Center, New York, USA

3University of Rochester, New York, USA

4GlaxoSmithKline, London, Vereinigtes Köngreich

Background: Belantamab mafodotin (belamaf; BLENREP) is a rst-

in-class, monomethyl auristatin F containing, B-cell maturation anti-

gen-directed antibody-drug conjugate. DREAMM-14 (NCT05064358)

investigates whether an improved benet/risk prole of single-agent

belamaf can be achieved by modifying the dose, schedule, or both, relative

to the approved dosing regimen (2.5 mg/kg Q3W) to reduce ocular events

without clinically meaningful decrease in ecacy.

Methods: is Phase II, randomized, open-label study includes adults

with RRMM and ≥3 prior lines of therapy (LOT). Patients are random-

ized into Arms A–D (n=40 each) and Arm E (n=20) in parallel stratied

by the International Staging System (I vs II vs III) and prior LOT (3 vs ≥4).

Belamaf is administered as follows - Arm A: 2.5 mg/kg Q3W; Arm B: 1.9

mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E:

1.9 mg/kg Q6W. Dose modications are based on oncology sta assess-

ment of ocular symptoms and visual acuity.Corneal ndingsare assessed

by eye care professionals (ECP).

Result: Patients in all Arms have response assessments, safety assess-

ments, and ophthalmic exams performed by ECP Q3W regardless of dos-

ing schedule. Ocular event-related dose modications (except in Arm E)

are guided by a modied Keratopathy and Visual Acuity scale.

Discussion: e primary endpoint is incidence of ocular events. Key sec-

ondary endpoints are ocular safety/tolerability, overall safety/tolerability,

pharmacokinetics, and ecacy outcomes. Follow-up for progression-free

survival is Q3W until progressive disease, start of new anticancer therapy,

withdrawal of consent, end of study, or death.

Conclusion: First patient rst visit was 04Mar22.

Funding: GSK (Study 209628); drug linker technology licensed from

Seagen Inc.; mAb produced using POTELLIGENT Technology licensed

from BioWa. Presented as TPS8073 at ASCO, Jun 3-7, 2022; submitted

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts174

MIC/Robotic

Poster

813

Stereotactic percutaneous electrochemotherapy as primary

approach for unresectable large HCC at the hepatic hilum

Lukas Luerken1; Ingo Einspieler1; Wibke Uller2; Christian Stroszczynski1

1Universitätsklinikum Regensburg, Radiologie, Interventionelle Onkologie,

Regensburg, Deutschland

2Universitätsklinikum Freiburg, Radiologie, Interventionelle Radiologie, Freiburg

im Breisgau, Deutschland

Background: Electrochemotherapy (ECT) is a non-thermal ablative tech-

nique that combines chemotherapy and the application of electric pulses

for reversible cell membrane electroporation. is method was recently

performed in the treatment of deep-seated liver tumors during open sur-

gery but experience about percutaneous ECT is rare and further develop-

ments like combination of percutaneous ECT with stereotactic navigated

devices may be very promising.

Methods: A 75-years old male patient with Child A liver cirrhosis pre-

sented with a 4.7 cm large central, unresectable HCC involving liver seg-

ments IV/VIII and a satellite HCC with 1.3 cm in segment V. e portal

vein showed thrombosis resulting in cavernous transformation while the

hepatic artery and the central bile ducts were located in close proximity to

the HCC. Stereotactic ECT of the central HCC and MWA of the satellite

was performed in one session under general anaesthesia.

Result: Magnetic resonance imaging (MRI) performed 24h aer the pro-

cedure conrmed complete devascularization of tumor and satellite. e

patient was discharged two days aer the procedure without complica-

tions. Contrast-enhanced MRI 6 weeks and 6 months aer ECT showed

complete response with no residual or recurrent HCC and without any

signs of damage of the central bile ducts or aection of the liver artery.

Discussion: e primary tumour was unresectable and not suited for

thermic ablation techniques such as RFA and MWA because of the close

proximity to the major blood vessels and bile ducts and was too large for

IRE. e possibility to navigate the percutaneous transhepatic approach

in accordance to the individual anatomy using a stereotactic navigation

system may be technically superior to ECT during open surgery or percu-

taneous techniques using uoroscopy.

Conclusion: Stereotactic percutaneous ECT has the potential to be used

as a treatment method for HCC with diameters of more than 4cm, even in

close proximity to critical structures like major blood vessels and central

bile ducts.

Disclosure Statement: e authors declare no conict of interest.

Molecular Pathology

Poster

181

Opportunities and Limitations - Use of Idylla assays in various

tumor samples in routine diagnostic settings

Sanga Mitra Boppudi1; Stefanie Scheil-Bertram1; Elisabeth Faust1;

Annette Fisseler-Eckho1,2

1Institute of Pathology and cytology, Helios Dr. Horst Schmidt Kliniken

Wiesbaden, Wiesbaden, Deutschland

2Gemeinschaftspraxis für Pathologie, Wiesbaden, Deutschland

Background: For cancer patients’ treatment, diagnostics concerning

tumor type and determination of molecular markers in short turnaround

time is very critical. e Biocartis-Idylla molecular assays are well estab-

lished in many laboratories for qualitative detection, short turnaround

time and routine screening of clinically relevant oncogenic mutations.

According to the manufacturer, all IVD-assays are recommended to use

only with FFPE tissue samples of 5-10µM dissections with at least 10%

tumor content.

Methods: In this current study, the dierent source materials used as input

material in the assay cartridges are (1) gDNA isolated from FFPE tissues,

cryomaterial, frozen tissue cuts, and HE stained slides. (2) tissue scratched

from normal 5µM and 2µM FFPE sections (3) tissue scratched from HE

slides (4) direct input of cryomaterial uid (5) direct input of tissue sec-

tion uid. Along with dierent input materials, the study also included

archival FFPE tissue sections dating from 15 years back. To check their

performance, all the IVD-Idylla assays catridges were also tested for dif-

ferent pan-tumor samples individually.

Results: All the assays tested with tissue scratched from FFPE/HE sec-

tions showed above 96% of accuracy, sensitivity, and specicity individ-

ually. is study indicates that minimum of 8ng/µl gDNA concentration

is required with at least 10µl input (80ng) for certainty of results. For use

of uids, a direct input of 20µl is recommended for better performance.

e Idylla assays also performed exceptionally well on the archival tissues

showing above 94% eciency. e use of IVD-labeled assays for other

solid tumors was also remarkable with more than 95% sensitivity and

specicity.

Discussion: e performance test and accuracy of Idylla assays with dif-

ferent tissue/source materials along with the recommended FFPE material

showed high eciency with certain limitations.

Conclusions: For use of Idylla assays, both qualitative and quantitative

applicability of dierent tumor materials could produce ecient results in

dierent diagnostic settings.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 175

381

Ki-67 gene expression

Sigrid Uxa; Paola Castillo-Binder; Robin Kohler; Konstanze Stangner;

GerdMüller; Kurt Engeland

Medizinische Fakultät, Universität Leipzig, Molekulare Onkologie, Leipzig,

Deutschland

Background: Ki-67 serves as a prominent cancer marker.

Results: We describe how expression of the MKI67 gene coding for Ki-67

is controlled during the cell cycle. MKI67 mRNA and Ki-67 protein are

maximally expressed in G2 phase and mitosis. Expression is dependent on

two CHR elements and one CDE site in the MKI67 promoter. DREAM

transcriptional repressor complexes bind to both CHR sites and down-

regulate expression in G0/G1 cells. Upregulation of MKI67 transcription

coincides with binding of B-MYB-MuvB and FOXM1-MuvB complexes

from S phase into G2/M. Importantly, binding of B-MYB to the two CHR

elements correlates with loss of CHR-dependent MKI67 promoter activa-

tion in B-MYB knockdown experiments. In knockout cell models, we nd

that DREAM/MuvB-dependent transcriptional control cooperates with

the RB Retinoblastoma tumor suppressor. Furthermore, the p53 tumor

suppressor indirectly downregulates transcription of the MKI67 gene.

is repression by p53 requires p21/CDKN1A.

Discussion: ese results are consistent with a model in which DREAM,

B-MYB-MuvB, and FOXM1-MuvB together with RB cooperate in cell

cycle-dependent transcription and in transcriptional repression following

p53 activation.

Conclusion: We present mechanisms how MKI67 gene expression fol-

lowed by Ki-67 protein synthesis is controlled during the cell cycle and

upon induction of DNA damage as well as upon p53 activation.

(Uxa et al. Cell Death and Dierentiation, 2021; in press)

Disclosure Statement: e authors declare no conict of interest.

554

Frequency of KRAS G12C plus co-mutations in solid tumors

and adequate test methods

Stefanie Schatz; Markus Falk; Markus Tiemann

Institut für Hämatopathologie Hamburg, Hamburg, Deutschland

Purpose: KRAS mutations were identied decades ago as oncogenic driv-

ers in various tumor entities. KRAS mutation analysis has recently gained

relevance since KRAS G12C specic and KRAS agnostic inhibitors have

nally entered clinical trials. For several years, many diagnostic institu-

tions have already routinely tested solid tumors for the presence of KRAS

mutations using various methods. ese data may prove important in

understanding the distribution of targetable KRAS alterations throughout

dierent tumor entities.

Methods: KRAS mutation status of solid tumor biopsies from patients

with advanced disease was collected retrospectively as assessed by hybrid

capture multi gene next generation sequencing (HC-NGS). Samples were

requested for routine driver mutation analysis between 2016 and 2021 and

data was retrospectively collected from our internal diagnostic documen-

tation soware.

Results: e majority of 2923 solid tumors were lung cancer biopsies,

but in addition colorectal-, mamma-, pancreatic carcinoma and oth-

ers. In 24.9% of tumor samples KRAS mutations aected codon G12X,

1.9% codon Q61X, A146X 0.1%, in 0.8% of samples other codons were

mutated. KRAS codon G12C has gained particular attention since the

advent of clinical trials investigating the ecacy of G12C specic KRAS

inhibitors. Among the >600 tumors harboring a G12X mutation, G12C

constituted the most prevalent amino acid exchange (47.0%), followed by

G12V (22.2%), G12D (16.3%), G12A (9.3%), G12S (2.0%), G12F/R (1.4%)

and G12L/E with each 0.2%.

Discussion: KRAS mutations, especially G12C is a common driver in

human cancers. Clinically relevant co-mutations like TP53, KEAP, STK11

and POLE have been discussed to inuence outcome and may gain impor-

tance in the future for molecular therapy stratication.

Conclusions: Although KRAS mutations are diagnostically assessible by

conventional test methods, we propose HC-NGS as a reasonable assay

to additionally detect co-mutations and potential resistance alterations

simultaneously in one assay.

Disclosure Statement: e authors declare the following: M. Tiemann:

Astra Zeneca Boehringer Ingelheim BMS MSD Novartis Roche Takeda

787

A Lesson from Lynch Syndrome: Five-Year Survival

of a Patient with Metastatic Pancreatic Cancer,

Post Ovarian and Breast Cancer and MLH1 Heterozygosity

Nurlan Abdullayev1; Jürgen Weitz2; Florian Lordick3; Thomas Brunner1

1Universtiätsmedizin Magdeburg, Klinik für Strahlentherapie, Magdeburg,

Deutschland

2Universitätsklilnikum Dresden, Klinik für Chirurgie, Dresden, Deutschland

3Universitätsklinikum Leipzig, Klinik für Hämatoonkologie, Leipzig, Deutschland

Aim: A patient with atypical Lynch syndrome (LS) and progressive pan-

creatic cancer (PDAC) surviving >5 yrs aer cured ovarian and breast

cancer posing a substantial therapeutic dilemma with lately evolving lung

mets and limited chemo tolerance.

Methods: e case is put into context of LS with MLH1 heterozygosity

and microsatellite stability (MSS).

Results: History: ovarian cancer @ 37 (resection, relapse aer 3 yrs, surgi-

cal salvage + adjuvant CDDP chemoRT), breast cancer @ 62 (BET: pT1c

pN0 G1 ER+/PR+;adj. RT and anastrozol), and PDAC @ 67 yrs with a

positive family history but stable microsatellites.PDAC was resected in

03/2016 (pT3 pN1(3/23) V1 L1 Pn1; K-Ras mt) plus adj. poorly tolerated

GEM. Local recurrence in 6/18 was treated by SBRT (12 x 5.5 Gy). A sin-

gular brain met was resected in 8/18 + adj. RT. SBRT of a single lung met

in 10/18. Multiple lung mets in 1/19 <= 6 mm, progressed by 3/19.From

4-8/19, 8 x FOLFIRINOX, cCR in 12/19. Local relapse of brain metin

03/20, re-SFRT with 7 x 5 Gy. Recurrent lung mets and FOLFOXnalIRI.

Last contact 08/21, stable performance status.

Conclusion: Patients with a pathogenic variant of MLH1 have a risk to

develop colorectal cancer (22%-53%), endometrial cancer (14-54%) and

other cancers e.g. ovarian (4%-20%), breast (5%-18%), pancreas (0.4%-

40%). Our patient had atypical LS with MLH1 heterozygosity but MSS.

erefore, immune checkpoint inhibitor therapy was not recommended

and the patient had excellent response to chemotherapy and radiotherapy.

However, salvage options for the patient are required. FOLFIRINOX rein-

duction was chosen. Alternatively, SBRT plus 1-2 courses of FOLFIRINOX

followed by ICI therapy would be an option; based on RT-induced sen-

sitization to ICI and increased mutation frequency aer RT of MSH1

decient tumour cells (Yan T et al. CCR 2009) as well as 5-FU / oxalipla-

tin-induced ICI sensitization (van der Kraak J Immunother Cancer 2016;

Kalanxhi E et al. Cancers 2020).

Disclosure Statement: e authors declare no conict of interest.

902

Evaluation of the AVENIO Tumor Tissue Comprehensive

Genomic Proling (CGP) Kit

Kay Hertel1; James Oughton2; Ulrich Schlecht3; Ina Vogl4;

Thomas Wieland4; Carlo Messina5

1Helios MVZ Pathologie, Erfurt, Deutschland

2Foundation Medicine, Inc., Cambridge, USA

3Signature Diagnostics GmbH, Potsdam, Deutschland

4Foundation Medicine GmbH, Penzberg, Deutschland

5Roche Diagnostics Solutions, Inc., Basel, Schweiz

Background: AVENIO Tumor Tissue CGP (AVENIO Kit) is a manual,

distributable, and research-use-only kit. It covers the same genomic

regions, 324 genes, as the FDA-approved FoundationOne CDx assay

(F1CDx). We wished to determine the agreement of both assays given the

dierent chemistry and bioinformatics pipelines.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts176

Methods: Aliquots of the same DNA extraction of 50 formalin-xed par-

an-embedded solid tumour tissue samples (majority breast [n = 15],

colon [n = 13] and prostate [n = 12]) served as input for both assays. e

AVENIO Kit was performed at Signature Diagnostics GmbH (Potsdam,

Germany) and F1CDx at Foundation Medicine GmbH (Penzberg,

Germany). Overall percent agreement (OPA), weighted kappa (WK), and

95% condence intervals (95% CI) were calculated.

Result: e AVENIO Kit had a median coverage of 1870X (460X with

F1CDx). In both assays, a median of 9.5 short variants per sample (range:

3–291; restricted to one exon: single/multiple nucleotide variants, inser-

tions, and deletions) were detected. OPA of short variants between assays

was 99.75% (95% CI: 99.71–99.79) and OPA of complex variants (crossing

exon borders: deletions, truncations, fusions, and rearrangements) was

99.41% (98.92–99.72). OPA of copy number alterations between assays

was 98.32% (95% CI: 97.97–98.63). WK of tumor mutational burden

(TMB) classications was 0.88 (95% CI: 0.78–0.98). Microsatellite stabil-

ity status was identical between assays in 45 samples; two were microsat-

ellite instability (MSI)-high and ve could not be evaluated by F1CDx.

WK of genome-wide loss of heterozygosity (gLOH) status was 0.82 (two

gLOH-high; 95% CI: 0.62–1.00).

Discussion: e higher coverage of the AVENIO Kit is a result of the

molecular, bioinformatics pipeline and the dierent chemistry. Agreement

decreases with the complexity of variations.

Conclusion: We observed a high degree of agreement between the

AVENIO Kit and F1CDx for all genomic variants and the genomic signa-

tures TMB, MSI, and gLOH.

Pres. at EFLM 2022

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Molecular Therapeutics

Poster

555

The University of Munich Virtual Molecular Tumorboard -

Patient Centered Care Meets Future Needs

Katharina Rühlmann1; Madeleine Flach1; Dorottya Biro1;

KathrinHeinrich2,3; Frank Ziemann2,3; Tobias Herold2,3; Louisa

vonBaumgarten4; Philipp Greif2,3; Irmela Jeremias3,5,6; Rachel Würstlein7;

Andreas Jung3,8; Jörg Kumbrink3,8; Thomas Kirchner3,8;

FrederickKlauschen3,8; Volker Heinemann1,2,3; Benedikt Westphalen1,2,3;

Korbinian Hasselmann2

1LMU University Hospital Munich, Comprehensive Cancer Center (CCC Munich

LMU), München, Deutschland

2LMU University Hospital Munich, Department of Medicine III, München,

Deutschland

3German Cancer Consortium (DKTK), Partner Site Munich, Deutschland

4LMU University Hospital Munich, Department of Neurology, München,

Deutschland

5Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital,

Department of Pediatrics, München, Deutschland

6Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit

und Umwelt (GmbH), Department of Apoptosis in Hematopoietic Stem Cells,

München, Deutschland

7LMU University Hospital Munich, Gynecologic Oncology Center, Breast Center

and Comprehensive Cancer Center Munich, Department of Obstetrics and

Gynecology, München, Deutschland

8LMU University Hospital Munich, Institute of Pathology, München, Deutschland

Background: Molecular Tumorboards (MTB) are important clinical

platforms in precision oncology. e MTB of the Comprehensive Cancer

Center at University of Munich was implemented in 2016 to discuss treat-

ment concepts based on molecular tumor proling. To provide broader

access to the University of Munich MTB, especially for Externals (eg.

community hospitals, local medical centers and practices) and readjusting

to the SARS-CoV2 pandemic, we transitioned from face-to face MTB to a

virtual setting (vMTB) in early 2020. e vMTB allows building loco-re-

gional expert networks for exchange on clinical studies and education and

helps to capture real world data across healthcare systems.

Methods: e vMTB takes place on a web-based platform. For security

purposes, the platform runs on in-house servers. However, we provide

a secure option to grant access rights to external users. e internal data

privacy guidelines, like anonymous case presentations and personalized

logins are adhered to.

Result: In 2020, 609 patients were discussed in the vMTB. Compared

with 2019 and despite the pandemic situation the clinical case number

increased by a factor of 1.5. Due to this rapid growth, the rhythm of

the vMTB changed on a weekly basis. 90/609 patients were enrolled by

Externals; this represents an increase from 6% to 15% of all patient regis-

trations compared with 2019. At present, the precision oncology program

cooperates with eleven partner sites mainly in southern Bavaria.

Discussion/Conclusion: e concept of virtualization removes geo-

graphical barriers, facilitates communication and opens the opportunity

to grow as an interdisciplinary network while simultaneously allowing

external patients to remain in their familiar treatment environment. e

vMTB helps closing the gap between healthcare sectors and allows an easy

access of internal and external partners to this innovative clinical struc-

ture. is holistic and patient-centered approach allows to further imple-

mentation of precision oncology into clinical practice.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

785

Whole Exome Sequencing to Select Targeted Therapies

forPatients with Breast or Gynecologic Cancer supported

byan Online Decision-Making Platform

Bernadette Jäger; Natalia Krawczyk; Dorothee Haas; Ellen Honisch;

Anne Kathrin Volkmer; Eugen Ruckhäberle; Dieter Niederacher;

Tanja Fehm

1Universitätklinikum Düsseldorf, Frauenklinik, Düsseldorf, Deutschland

Background: e aim of this proof-of-concept study was to select therapy

targets or dene potential therapy resistance and safety issues in patients

with advanced breast (BC) or gynecologic cancer (GC). e project was

supported by an online decision-making platform (MH guide®, Molecular

Health, Heidelberg) to simplify data interpretation for daily clinical

routine.

Methods: We established next generation sequencing (NGS) based whole

exome sequencing (WES) of patients with advanced BC (n=44) of any

subtype or GC (n=8). Patients with GC suered from ovarian n=2, vulva/

vaginal n=3, endometrial n=2 or cervical cancer n=1. WES was performed

from most recent tumor samples (metastatic lesions or primary tumors)

and corresponding blood samples (germline). e indication for study

participation and the discussion of the results took place in our molecular

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 177

tumor conference. Gene alterations (GA) were categorized in “eective”,

“ineective” and “safety” according to MH guide® criteria.

Result: In BC patients, we detected 44 potentially eective GA (mutations)

in 19 dierent genes. Most GA were found in TP53 (n=7), PIK3CA (n=6)

and CDH1 (n=5). BRCA1 and BRCA2 were altered in 2 and 5 patients,

respectively. PARP- and PI3K- inhibitors were recommended accordingly.

High TMB and MSI were discovered in 6 and 15 patients. GC patients had

15 potentially eective GA in 12 dierent genes with CHEK2 and KRAS

mutated in two patients. “Ineective” and “safety” GA were analyzed as

well and will be reported in the same way.

Discussion: WES is technically feasible but selecting targeted therapies in

advanced BC and GC based on WES results is still challenging. Long time

intervals occur until results are reported and the procedure is cost-inten-

sive. In addition, for many of the “eective” gene alterations detected in

our collective there is still no approved treatment option.

Conclusion: Consequently, we established an in-house gene panel (ther-

apy-resistance-toxicity-panel (TRTP)) to quickly choose and validate tar-

geted therapies and optimize BC and GC treatment in future.

Disclosure Statement: e authors declare no conict of interest.

840

Tepotinib + getinib in patients with EGFR-mutant NSCLC

with MET amplication (METamp): nal analysis of INSIGHT

Chong Kim Liam1; Azura Rozila Ahmad2; Te-Chun Hsia3; Jianying Zhou4;

Dong-Wan Kim5; Ying Cheng6; Shun Lu7; Sang Won Shin8; James

Chih-Hsin Yang9; Yiping Zhang10; Jun Zhao11; Rolf Bruns12; Andreas

Johne13; Yi-Long Wu14

1University of Malaya, Faculty of Medicine, Kuala Lumpur, Malaysia

2Beacon Hospital, Selangor, Malaysia

3China Medical University Hospital, Taichung City, Taichung City, Taiwan

4The First Aliated Hospital, Zhejiang University, Hangzhou, China, VR

5Seoul National University Hospital, Seoul, Korea, Dem. People’s Rep. of

6Jilin Province Cancer Hospital, Changchun, China, VR

7Shanghai Chest Hospital, Shanghai, China, VR

8Korea University Anam Hospital, Seoul, Korea, Dem. People’s Rep. of

9National Taiwan University Hospital, Taipei, Taiwan

10Zhejiang Cancer Hospital, Hangzhou, China, VR

11Beijing Cancer Hospital, Beijing, China, VR

12Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Deutschland

13Global Clinical Development, Merck Healthcare KGaA, Darmstadt,

Deutschland

14Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital

and Guangdong Academy of Medical Sciences, Guangzhou, China, VR

Background: In the INSIGHT trial primary analysis (NCT01982955;

median follow-up: 21.8 months), tepotinib (a potent, highly selective,

once daily [QD] MET inhibitor) + getinib improved ecacy vs chemo-

therapy (CT) in patients (pts) with EGFR-mutant (m) NSCLC and resis-

tance to anti-EGFR therapy due to METamp (Wu et al, Lancet Respir Med

2020). Here we report nal analyses from INSIGHT (data cut-o: Sept 3,

2021; median follow-up: 57.5 months).

Methods: Pts with EGFR-m (T790M-negative) NSCLC and anti-EGFR

resistance, with MET gene copy number (GCN) ≥5 and/or MET:CEP7

≥2 by FISH (METamp), and/or MET IHC 2+/3+ (MET overexpression),

were randomized to tepotinib 500 mg (450 mg active moiety) + getinib

250 mg QD or CT. Primary endpoint was progression-free survival (PFS)

per investigator. Preplanned analyses evaluated pts with METamp.

Result: In 19/55 randomized pts (34.5%) with METamp (GCN ≥5, n=18;

MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), median age was 60.4 years,

68.4% were never-smokers, and prior EGFR inhibitors were getinib

(57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). Median

duration of tepotinib + getinib was 11.3 months (range: 1.1–56.5), with

treatment duration >1 year in 6 pts (31.6%) and >4 years in 3 pts (15.8%).

Two pts continued treatment outside the study. Tepotinib + getinib

(n=12) improved outcomes vs CT (n=7). Respectively, median PFS was

16.6 vs 4.2 months (HR=0.13; 90% CI: 0.04, 0.43), median overall survival

(OS) was 37.3 vs 13.1 months (HR=0.10; 0.02, 0.36), objective response

rate was 67% vs 43% (odds ratio=2.67; 0.37, 19.56), and median dura-

tion of response was 19.9 (7.0, not estimable [ne]) vs 2.8 months (2.8, ne).

Treatment-related Grade ≥3 AEs occurred in 7 pts (58.3%) with tepotinib

+ getinib and 5 (71.4%) with CT. In pts with MET IHC 3+ (n=34; includ-

ing 17 pts with METamp), tepotinib + getinib also improved PFS (HR

0.35; 90% CI: 0.17, 0.74) and OS (HR 0.44; 0.23, 0.84) vs CT.

Conclusion: Tepotinib + getinib improved PFS and OS vs CT in pts with

EGFR-m NSCLC with METamp. INSIGHT 2 is evaluating tepotinib +

osimertinib in this setting

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

929

Targeting BRD4 potentiates YB-1 dependent oncolytic

adenovirus XVir-N-31 through E1A12S-mediated redirection

of cellular transcription machinery to viral genomes

Florian G. Klein1; Felicia Segeth2; Klaus Mantwill1; Viktoria Bondarets1;

Marvin Thielert3; Matthias Mann3; Jürgen E. Gschwend1; Andreas Kolk2;

Roman Nawroth1; Per Sonne Holm2,4

1Klinikum Rechts der Isar, Technical University of Munich, Department of

Urology, Munich, Deutschland, 2Medical University of Innsbruck, Department

of Oral and Maxillofacial Surgery, Innsbruck, Österreich, 3Max Planck Institute of

Biochemistry, Proteomics and Signal Transduction, Martinsried, Deutschland,

4XVir Therapeutics GmbH, Munich, Deutschland

Background: e epigenetic reader protein BRD4 orchestrates eukaryotic

and adenoviral gene expression via the RNA-Polymerase II machinery.

XVir-N-31, a YB-1 dependent oncolytic adenovirus with a deletion of

the adenovirus E1A13S protein that binds to the eukaryotic cyclin-de-

pendent kinase 9 (CDK9), shows reduced transactivation activity and

consequently reduced replication and cancer cell killing capacity. In this

study, we evaluated the role of BRD4 in XVir-N-31 gene expression, viral

genome replication and subsequent tumor cell killing.

Methods: We investigated XVir-N-31 and targeting of BRD4 via inhibi-

tion, protein degradation, genetic depletion or acquired resistance in vitro

and in a nude mice model in vivo. Characterization of the underlying

molecular mechanism was performed by protein overexpression, viral

transactivation assays, Co-IP and ChIP immunogenic pull-down assays,

and LC-MS proteomics analysis.

Result: Inhibition of BRD4 by the small molecule JQ1 unexpectedly

enhances XVir-N-31 gene expression and subsequently viral genome

replication, particle formation, and oncolysis. At the molecular level,

this occurs via enhanced association of the adenovirus protein E1A12S,

present in XVir-N-31, with CDK9, an activator of RNA-Pol 2 elongation.

In contrast, BRD4 depletion by siRNA prevented adenovirus induced

S-phase progression, minimizing the enhancement of JQ1 on viral

replication.

Discussion: Here, we discovered that BRD4, unlike in other viruses, is

not directly involved in adenoviral gene expression but is necessary

for the induction of S-phase, which promotes adenoviral replication.

Furthermore, inhibition of BRD4-binding to acetylated histones by

JQ1, which facilitates E1A12S binding to CDK9, indicates that BRD4 is

involved in regulating the transactivation capacity of E1A-proteins.

Conclusion: Combining the oncolytic adenoviruses XVir-N-31 with

BRD4 inhibition oers a novel approach to enhance the lytic eect of

XVir-N-31 in a clinical setting.

Disclosure Statement: P.S.H. is co-founder of XVir erapeutics GmbH.

Disclosure Statement: e authors declare the following: P.S.H. is co-founder of

XVir erapeutics GmbH. All other authors declare no competing interests.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts178

1024

Combined targeting of bromodomain protein BRD4 and

RB /E2F axis leads to highly synergistic cell killing by YB-1

dependent oncolytic virus in HNSCC

Felicia Segeth1; Florian Klein2; Eva Magdalena Beck1; Klaus Mantwill2;

Jürgen Gschwend2; Roman Nawroth2; Andreas Kolk1; Per Sonne Holm1,2,3

1Department of Oral and Maxillofacial Surgery, Medical University Innsbruck,

Innsbruck, Österreich

2Department of Urology, Klinikum rechts der Isar, Technical University of

Munich, München, Deutschland

3XVirTherapeutics GmbH, München, Deutschland

Background: e entry of oncolytic viruses (OVs) into clinical applica-

tion opens groundbreaking changes in current and future treatment reg-

imens. However, despite their potent anti-cancer activity in vitro, clinical

studies revealed limitations of OVs as monotherapy. e same applies to

CDK 4/6 inhibitors (CDK4/6i) and BRD4 inhibitors (BETi) targeting the

cell cycle. In this study, we evaluated the anti-tumoral eect of XVir-N-31,

an YB-1 dependent oncolytic adenovirus, in combination with Ribociclib,

a CDK4/6 inhibitor, and JQ1, a BRD4 inhibitor, in vitro in a panel of

HNSCC cell lines.

Methods: HNSCC cell lines Cal33, Fadu and SAS were used. Ribociclib

was used as a CDK4/6- and JQ1 as BRD4 inhibitor. Replication and gene

expression of XVir-N-31 was measured by RT-qPCR, protein expression

by western blotting, and cell lysis by SRB assays. Furthermore, we per-

formed ChIP-PCR and RNA-Polymerase II activation assay to determine

RNA-Polymerase activity.

Result: Treatment with CDK4/6i and BRD4i increase viral gene expres-

sion, viral genome replication, particle formation and leads to highly syn-

ergistic cell killing of XVir-N-31 in infected HNSCC cells.

Discussion: Our data show that in spite of the opposing roles in aecting

the cell cycle, the combination of oncolytic adenovirus XVir-N-31 with

CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore,

additional molecular analyses on this subject demonstrate that the pos-

itive transcription elongation factor P-TEFb plays a decisive role in this

regard.

Conclusion: e combination of CDK4/6i & BETi and XVir-N-31 is an

attractive strategy to achieve substantial cancer cell killing and is highly

suitable for clinical testing.

Disclosure Statement: e authors declare no conict of interest.

Novel Agents/Early Clinical Trials

Poster

690

ZENYTH-ESO Substudy 1 (GSK3901961), Cohort 1: a rst-in-

human study to assess the safety and recommended phase

II dose of next generation NY-ESO-1-specic TCR T-cells in

HLA-A*02 patients with non-small cell lung cancer

Martin Wermke1; Roland Ullrich2; Jerey Yachnin3; Stephan Mielke4;

Reema Patel5; Melinda L Yushak6; Adam J. Schoenfeld7; Jayesh Desai8;

Mehmet Altan9; Sandra P. D’angelo10; Jonathan Noujaim11;

John B.A.G. Haanen12; Benjamin Powers13; Thomas Faitg14; Wenlei Liu15;

Nitin Patel15; Dejka M. Araujo16

1Universitätsklinikum Carl Gustav Carus

2Klinikum der Universität Köln, Köln, Deutschland

3Karolinska University Hospital and Institutet, Karolinska Comprehensive Cancer

Center, Stockholm, Schweden

4Karolinska University Hospital and Institutet, Karolinska Comprehensive Cancer

Center, Stockholm, Schweden

5Markey Cancer Center, University of Kentucky, Lexington, USA

6Winship Cancer Institute at Emory University, Department of Hematology and

Medical Oncology, Atlanta, USA

7Memorial Sloan Kettering Cancer Center

8Peter MacCallum Cancer Centre, Melbourne, Australien

9MD Anderson Cancer Center

10Memorial Sloan-Kettering Cancer Center, New York, USA

11Institut D’Hématologie-Oncologie, Hôpital Maisonneuve-Rosemont

12Antoni van Leeuwenhoek Ziekenhuis

13University of Kansas Medical Center, Division of Hematology/Oncology,

Department of Internal Medicine, Kansas City, USA

14GlaxoSmithKline

15GlaxoSmithKline, Collegeville, USA

16MD Anderson Cancer Center, Manseld, USA

Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autolo-

gous T cell therapy expressing an anity-enhanced T cell receptors (TCR)

to improve recognition of cancer cells expressing NY-ESO-1 and/or

LAGE-1a. It is being evaluated in non-small cell lung cancer (NSCLC)

[1], where NY-ESO-1 and LAGE-1a expression occur in 20–30% and 16%

of tumors, respectively [2-3]. Additional modications are being incor-

porated into next generation cell therapies to improve therapeutic poten-

tial. GSK3901961 incorporates the same anity-enhanced T-cell receptor

as lete-cel and in addition expression of the CD8α chain to induce sta-

bilization of TCR-HLA class I interaction on CD4+ T cells to enhance

T-cell persistence and helper functions, and potentially enhance activity

of tumor-specic immune response.

Within a rst-in-human master protocol (NCT04526509, ZENYTH-

ESO), substudy 1 will investigate GSK3901961 in patients with advanced

non-small cell lung cancer.

Methods: Substudy 1 has two stages; initial dose conrmation and dose

expansion. Key eligibility criteria include age ≥18 yrs, Stage IV NSCLC.

Patients must be HLA-A*02:01, *02:05, or *02:06-positive, and express

NY-ESO-1/LAGE-1a on tumor biopsy. Patients with and without action-

able genetic aberrations are eligible if they have received ≥1 prior lines(s)

of standard of care therapy.

Primary endpoints: safety (adverse events) and tolerability (dose-

limiting toxicities). Secondary endpoints: investigator-assessed over-

all response rate, duration of response, maximum transgene expansion

(Cmax), Tmax, and AUC(0-t). Analyses will be descriptive. e master protocol

is open for recruitment.

Results: Funding: GSK (209012, NCT04526509).

Discussion: Previously presented at WCLC 2021.

Conclusions: is study is recruiting. is substudy will evaluate the

safety and ecacy of GSK3901961 in NSCLC.

References:

1. Reckamp KL, et al. Ann Oncol 2019;30(Suppl_5):v657–8

2. Gnjatic S, et al. Adv Cancer Res 2006;95:1–30

3. Kim YD, et al. Int J Mol Med 2012;29:656–62

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 179

Novel developments: Cytotoxic Chemotherapy

Poster

853

Local treatment of conjunctival melanomas using repetitive

electrochemotherapy – in vitro analysis of antitumor

eectiveness in 3D tumor models

Joana Heinzelmann1; Udo Siebolts2,3; Sarah Coupland4; Arne Viestenz1

1Universitätsklinikum Halle (Saale), Klinik für Augenheilkunde, Halle (Saale),

Deutschland

2Universitätsklinikum Halle (Saale), Institut für Pathologie, Halle (Saale),

Deutschland

3Universitätsklinikum Köln, Institut für Pathologie

4Liverpool of University, Molecular & Clinical Cancer Medicine, Vereinigtes

Königreich

Local treatment of conjunctival melanomas using repetitive elec-

trochemotherapy – in vitro analysis of antitumor eectiveness in 3D

tumor models

Authors: Joana Heinzelmann, Udo Siebolts, Sarah Coupland, Arne

Viestenz

Background: Conjunctival melanoma (CM) is a rare ocular tumor.

Despite dierent treatment options, CM has a high rate of local recur-

rences as well as a worse survival rate. Novel therapy options are needed

to improve the prognosis of CM.

Electrochemotherapy (ECT) is a combination of chemotherapy and

electroporation for local therapy of tumors. In treatment of various can-

cers like cutaneous melanoma and subcutaneous tumor lesions, ECT is a

promising clinical veried therapy. is study proved the eectiveness of

repetitive application of ECT on CM.

Methods: Tumor spheroids of three CM cell lines were treated repetitively

with ECT using chemotherapeutic agent bleomycin on day 3, 5 and 7 of

culture (3xECT). Application of bleomycin alone (CT) as well as electro-

poration alone (EP) served as controls. Cytotoxic eect was measured at

day 10 by determination of viability, spheroid growth, proliferation capac-

ity and apoptosis induction. Spheroid outgrowth rate was measured up to

80 days of reculturing.

Result: Compared to controls, spheroid size and viability was signi-

cantly reduced aer 3xECT treatment. 3xECT treatment of CM spher-

oids is associated with decreased proliferation capacity (down to 8%) and

increase in apoptotic cells. In the majority of 3xECT treated spheroids,

no viable and proliferating cells were detected. Only 30-40% of 3xECT

treated spheroids exhibited single outgrowing cells and thereby, with a

delay of time up to 38 days.

Discussion: 3xECT application eectively induce cytotoxic eect on CM

spheroids via inducing apoptosis, inhibition of proliferation and conse-

quently a small percentage of surviving tumor cells. Further studies are

needed to establish a CM adapted ECT protocol.

Conclusion: ese data supports the hypothesis that 3xECT results in an

improved antitumor eectiveness in CM and could be used as alternative

therapy option.

Disclosure Statement: e authors declare no conict of interest.

983

Development of halido(NHC)gold(I) complexes as antitumor

agents: Investigations on the reactivity with components of

cellular medium and their inuence on cytotoxicity

Paul Kapitza; Amelie Scherer; Ronald Gust

Universität Innsbruck, Pharmazie, Pharmazeutische Chemie, Innsbruck,

Österreich

Background: Auranon represents a gold(I)-containing drug that was

approved in 1985 for the treatment of rheumatoid arthritis. e primary

mode of action postulated for Auranon involves its property to disrupt

the reduction/oxidation system within the cell. erefore, the complex

also causes unspecic cytotoxic eects in malignant and non-malignant

cells.

Methods: In order to increase the tumor selectivity, N-heterocyclic car-

bene (NHC) complexes of the halido(NHC)gold(I) (halido = Cl- 1, Br- 2,

I- 3) and [(NHC)2Au(I)]+ (4) type were developed and tested for anti-

tumor activity in vitro against numerous wildtype and corresponding

resistant cancer cell lines (A2780, A549, MCF-7, K562). We analyzed the

components in cell medium and studied the reaction with (NHC)gold(I)

compounds 1-4 using HPLC experiments.

Result: e compounds showed improved (4-fold) ecacy on the cispla-

tin-resistant ovarian cancer cell line A2780cis (IC50: Cisplatin (9.80 µM)

> 1 (4.97 µM) > 2 (3.95 µM) > 3 (0.45 µM) > 4 (0.03 µM)) compared

to A2780wt. Furthermore, the cytotoxic eects were only marginally in

non-cancerous SV-80 cells. e gold complexes interact very fast with thi-

ol-containing molecules. Complete replacement of the halogen at the gold

center in physiological NaCl solution yielding the chlorido(NHC)gold(I)

was demonstrated for 2 and partially for 3. e latter underwent also a

ligand scrambling to the higher active 4. e reaction products were iso-

lated and their participation on the cytotoxic eect was conrmed.

Discussion: As other metal-based drugs, the complexes interact with

intracellular targets upon ligand exchange reactions. Already in cell cul-

ture medium potential nucleophiles are present. If the complexes are

transformed in the medium prior to the cellular uptake, the antitumor

eects cannot be ascribed to the original complex.

Conclusion: e data from this study clearly demonstrate that the assess-

ment of the biological activity of gold(I) complexes in tumor therapy has

to be done with care, because degradation products participate on the bio-

logical activity.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts180

Nursing in Oncology

Poster

Implementierung einer Advanced Practice Nurse (APN) im

Brustzentrum des LMU Klinikums München

Kristina Lippach1; Inge Eberl1; Rachel Würstlein2

1Stabsstelle Personalentwicklung und Pegewissenschaft, LMU Klinikum

München, München, Deutschland

2Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum

München, Brustzentrum und CCC München, München, Deutschland

Background: Der Einsatz von oralen Tumortherapien führt zu veränder-

ten Versorgungsbedarfen und zu Veränderungen im pegerischen

Tätigkeitsfeld.

Methods: Mittels Evaluationsstudie im Mixed-Methods-Design wurden

die Perspektiven von Pegenden, Ärztinnen und Patientinnen zu Eekten

einer APN-Rolle erhoben. Als patientenbezogene Outcomes wurden in

einem prä-post-Design die gesundheitsbezogene Lebensqualität und die

Informiertheit mittels EORTC-QLQ-C30 und EORTC-QLQ-INFO25

betrachtet.

Result: Herausfordernd in der Implementierung waren die

Akzeptanz der neuen Pegerolle, die Einbindung in ärztliche und

pegerische Versorgungsstrukturen und die Auswahl erweiterter

Pegetätigkeiten. Patientinnen mit APN schätzten die Zufriedenheit

mit Versorgungsprozessen, dem Nebenwirkungsmanagement und der

psychosozialen Betreuung positiver ein. Informationen zur Behandlung

(t0=64,02, t1= 74,18), weiterführende Versorgungsangebote (t0=45,38,

t1= 65,69), Möglichkeiten des Selbstmanagements (t0=59,70, t1= 82,35)

und Zufriedenheit mit Informationen (t0=73,85, t1= 90,19) wurden in der

APN-Gruppe deutlich besser bewertet.

Discussion: Während die Rolle der APN bei Ärzten und Patientinnen

akzeptiert wurde, zeigten die Pegenden deutliche Vorbehalte, die

sich negativ auf die intraprofessionelle Kooperation auswirkten.

Patientenbezogene Outcomes, wie Zufriedenheit und Informiertheit,

wurden analog vorheriger Studien deutlich positiver bewertet als ohne

APN. Patientinnen waren anfangs skeptisch gegenüber der Betreuung

durch eine APN, was sich im Verlauf veränderte hin zu Akzeptanz und

Wertschätzung.

Conclusion: Die patientenbezogenen Eekte zeigten, dass das

Implementierungsziel mit der APN erreicht wurde. Perspektivisch kann

die APN durch ihre Kompetenzen und ihre Arbeitsweise einen Beitrag

zur Patientenzufriedenheit und -sicherheit aber auch zu organisatio-

nalen Entwicklungen, wie dem Magnet-Gedanken leisten. Gerade in

der Onkologie bildet eine spezialisierte APN ein optimales Bindeglied

zwischen allen Beteiligten.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Onkologische Pege zwischen Fachlichkeit,

Qualitätsanforderungen und Pegemanagementstrategien in

der Uniklinik Köln

Johannes Bösche1; Dennis Nano1; Barbara Starbatty2; Steen Krebs2;

Barbara Strohbücker3

1Uniklinik Köln, Pegedirektion, Pegedienstleitung Allgemeinpege, Köln,

Deutschland

2Uniklinik Köln, Centrum für Integrierte Onkologie (CIO) Aachen Bonn Köln

Düsseldorf, Köln, Deutschland

3Pegedirektion, Stabsabteilung Pegepraxis und Entwicklung, Köln,

Deutschland

Background: Fachweitergebildetes Pegepersonal für alle Abteilungen des

Onkologischen Zentrums zu gewinnen und die Zertizierungsvorgaben

zu erfüllen stellen angesichts des Personalmangels eine permanente

Herausforderung dar. Um Rahmenbedingungen und Umsetzung sicher-

zustellen, ist eine enge Zusammenarbeit von Fachpege, Qualitäts- und

Pegemanagement wichtig.

Methods: In Jour Fixen von Fachpege, QM und Pegemanagement

werden Probleme und Ergebnisse aus Audits, Patientenbefragungen

und Praxis analysiert und Lösungsstrategien erarbeitet. Zur klinikweiten

pegefachlichen Versorgung wird eine Kombination aus zentraler und

dezentraler Expertenstruktur mit eigenen Aufgabenprolen entwickelt.

Result: Wichtigstes Ergebnis dieser Zusammenarbeit ist das Modell einer

Kombination aus zentraler und dezentraler Personaleinsatzstruktur.

Hierfür wurden Aufgabenprole, Rahmenbedingungen und Strukturen

entwickelt. Die Zentrale Onkologische Fachpege wird dezentral in den

Krebszentren um onkologische Pegeexperten erweitert. Sie sollen als feste

Ansprechpartner für die Patienten entlang des Behandlungspfades fungi-

eren. Darüber hinaus konnten Pegevisiten und Fallbesprechungen nach-

haltig implementiert werden und stellen die Zertizierungsanforderungen

sicher.

Discussion: Die Zusammenarbeit von Fachpege, QM und

Pegemanagement fördert das gegenseitige Verständnis und erö-

net Handlungsspielräume. Die Kombination aus zentral und dezen-

tral eingesetzten Pegeexperten, ermöglicht eine ächendeckende

Patientenversorgung nach aktuellem Stand des Wissens. Verbindlichkeit

in Bezug auf Rolle und Aufgaben stärkt die Arbeitszufriedenheit.

Conclusion: Ein funktionierendes Netzwerk zwischen Fachpege,

Qualitäts- und Pegemanagement steuert zentral und steht im kontinui-

erlichen Dialog mit den Krebszentren. Die enge Zusammenarbeit scha

nachhaltig pegerische Rahmenbedingungen, die eine fachpegerische

Versorgung der onkologischen Patienten in konservativen und operativen

Bereichen sicherstellen.

Disclosure Statement: e authors declare no conict of interest.

200

Improving the quality of oncological care at the University

Krukenberg Cancer Center Halle (KKH) through oncological

nursing visit (ONV)

Jana Tietl; Lysanne Götze; Susann Schulze; Haifa Kathrin Al-Ali

Krukenberg Krebszentrum Halle, Universitätsklinikum Halle, Halle (Saale),

Deutschland

Introduction: e Oncological Center (KKH) of the University Hospital

Halle (UKH) is certied by the German Cancer Society since 2017. To

improve in-patient (pat) oncology care, ONVs were established. We pres-

ent the impact of ONVs on pat management in the Head and Neck Cancer

(HNC) Center of the KKH.

Methods: ONVs were established in 2018 as a centralised digital council

service of the KKH for all nurses caring for cancer pats at the UKH. In the

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 181

presence of ward nurses, ONVs were conducted at the bedside by certied

KKH oncological nurses. Each pat was handed a folder with all facets of

cancer care. is analysis includes 236 pats with head and neck tumors

from 2019 and 2020. Pats who received ONVs (n=96; group A) were com-

pared to pats without ONVs (n=147; group B).

Results Pat characteristics were similar in the two cohorts in terms of age

[median 63.5 (range 40-95)] years (y) for A vs 64, (range 43-90) y for B

and the Karnofsky Index (80%, in A vs 90%, in B. Group A included 87/96

(91%) newly diagnosed and 9% relapse/refractory pat. Similarly, in B

129/147 (87%) pat were newly diagnosed and the remaining 18 pats were

suering from relapse/refractory HNC. Although symptoms were doc-

umented by the standard nursing sta, in the ONVs further less specic

symptoms could be revealed. Dry mouth, loss of appetite, fatigue, psycho-

logical problems, and emotional distress were documented in 95%, 39%,

40%, 95%, and 32% In A vs 19%, 1%, 7%, 38%, and 7% in B, respectively.

With ONVs, more detailed advise and management tips for pat regarding

dierent medical problems such as tracheostoma, PEG, mouth, and skin

care could be given. Additionally, psychological support could be oered

to 98% of pats in A compared to 34% in B. Contact to pat advocacy groups

was also possible.

Conclusions With the implementation of ONVs, a high level quality of

cancer care is possible. Sucient time and extra qualied personal res-

sources allow a much closer look to the individual pat, the identication

of physical and mental needs, and the initiation of the appropriate mea-

sures. e impact of ONVs on long-term outcome of cancer needs to be

analysed.

Disclosure Statement: e authors declare no conict of interest.

472

Onkologische Pegevisiten an der Chirurgischen Klinik am

UKHD

Romy Fiedler1; Claudia Ohlrogge1

1Universitätsklinikum Heidelberg, Chirurgische Klinik, Arbeitsgruppe

Onkologische Pege, Heidelberg, Deutschland

Background: Im Rahmen der Zertizierung als onkologisches

Fachzentrum wurde an der Chirurgischen Klinik des

Universitätsklinikums Heidelberg die Arbeitsgruppe (AG) Onkologische

Pege gegründet, um die pegerische Versorgung onkologischer

PatientInnen weiter zu verbessern. Ein wichtiges Instrument dabei stellen

onkologische Pegevisiten dar.

Methods: Die AG besteht aus 5 erfahrenen Fachgesundheits- und

KrankenpegerInnen für Palliative Care und/ oder Onkologie. Einmal

pro Woche visitiert eine Pegekra PatientInnen mit potenziellem und

bestehendem onkologischem Beratungsbedarf. Schwerpunkte hier-

bei sind neben der persönlichen Krankheitsbewältigung emen wie

weitere erapiemöglichkeiten, Ernährung, Schmerztherapie oder

auch die Anbindung an ambulante Palliativteams. Des Weiteren stellt

die Pegevisite eine Schnittstellenverknüpfung im interdisziplinären

Teamdar.

Result: In den letzten zwei Jahren konnten über 90 onkologische

Pegevisiten durchgeführt werden. In 2/3 der Fälle wurde zu pegerel-

evanten emen beraten. 1/3 der Visiten dienten als erleichternde

Gespräche ohne beratende Inhalte.

Discussion: Chirurgische PatientInnen können von onkolo-

gischen Pegevisiten protieren. Der Erfolg hängt u.a. vom

Zustand der Betroenen am Visitentag sowie dem Grad der

Krankheitsverarbeitungab.

Conclusion: Onkologische Pegevisiten sind ein Instrument zur

Ermittlung von Unterstützungsbedarf und zur Abstimmung pegerischer

Ziele und Maßnahmen. Dabei können aktuelle Pegeprobleme, notwen-

dige Maßnahmen für die Zeit nach der Entlassung oder die persönliche

Belastung thematisiert werden.

Indication of source

1 Lippach, K; Kelber, S; Gutekunst, S (2018): Onkologische Pegevisite und

Fallbesprechung – praktische Umsetzung. Onkologische Pege, 4: 48–54

2 Maio, G (2020): Zuwendung als Heilmittel gegen das Leiden. Dem leidenden

Menschen begegnen. CNE.fortbildung 2020; 13: 10-12

Disclosure Statement: e authors declare no conict of interest.

494

Aromapege: Rosenhydrolat zur Hautpege unter

Strahlentherapie

Bettina Noack1; Renate Fuhr2

1Tübingen, Radioonkologie, Pegeambulanz, Tübingen, Deutschland

2Universitätsklinikum Tübingen, Pegedirektion, Tübingen, Deutschland

Purpose: Unter Strahlentherapie pegen viele Patient*innen ihre

Haut intensiv mit fetthaltigen Salben und verstärken so ungewollt

durch „Überpegung“ häug das dermatologisch therapiebedingte

Krankheitsbild. Bei der Verwendung von Rosenhydrolat ist bekannt,

dass es die Hauttoxizität durch seine entzündungshemmenden und

wundheilenden Eigenschaen verringert und der Wohlgeruch das

Allgemeinbenden während der Strahlentherapie unterstützen kann.

Methods: In der radioonkologischen Pegeambulanz (PA) des

Universitätsklinikums Tübingen wurden n=27 Tumorkranke in einer

Anwendungsbeobachtung (AWB) mit Rosenhydrolat (RH) untersucht.

Nach unauälligem Armbeugentest – wurde das RH 3-4 x täglich im

Bestrahlungsgebiet angewendet. Zusätzliche Hydrierung durch Cremes

oder Öle war bei Bedarf möglich. Parameter: RT-Hauttoxizität, Wohlgefühl

Haut, psychisches Wohlbenden und Besserung des Juckreizes.

Results: 100% (n=27) der Erkrankten empfanden den Du des RH´s

als angenehm. Bei allen war der Armbeugentest nach der Anwendung

negativ. 70,4% (n=19) empfanden die Anwendung als angenehm für

Haut und Psyche. 51,9% (n=14) der Anwender*innen verspürten eine

Verbesserung des Juckreizes. 25,9% (n=7) der Patient*innen brachen die

Anwendung bei einer RT Toxizität EORTC/RTOG in St. 3 ab. 29,6% (n=8)

der Patient*innen stellten sich nicht mehr in der PA vor.

Discussion: Aufgrund der sehr kleinen und heterogenen Stichprobe sind

die Ergebnisse nur eingeschränkt aussagekräig; die AWB zeigt jedoch

tendenziell ein vielversprechender Outcome, bei der ebenfalls überwieg-

end über die traditionelle, nicht-evidenzbasierte Anwendung von RH in

der Literatur berichtet wird.

Conclusion: In der AWB zeigte die Applikation von RH im

Bestrahlungsfeld vorwiegend positive Ergebnisse. Für ein repräsenta-

tives Ergebnis ist eine umfassendere Studie erforderlich, die derzeit in

Planungist.

Disclosure Statement: e authors declare no conict of interest.

642

Detecting Stress and Stressors at the Workplace in Palliative

Care – The DiPa Study

Aaron Seehausen1; Carolin Schneider1; Wencke Chodan2; Florian

Höpfner2; Hugo Murua Escobar1; Christian Junghanß1; Mario Aehnelt2

1Rostock, Department of Medicine, Clinic III – Hematology, Oncology, Palliative

Medicine; Rostock University Medical Center, Rostock, Deutschland

2Rostock, Fraunhofer Institute for Computer Graphics Research, Rostock,

Deutschland

Background: Nurses in palliative care are exposed to particular stress

through confrontation with grief, dying and death. As a result, they are

at higher risk for physical or mental disorders such as burnout. e gen-

eral and individual causes are not well researched. e DiPa study aims at

nding and reducing typical stressors in a palliative care unit.

Methods: Nurses at the palliative care unit of the Rostock University

Medical Center were voluntarily enrolled. ey were equipped with a wrist

band to continuously measure bioparameters in combination with record-

ing environmental parameters through additional technical equipment.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts182

Data was generated during each work shi for 6 weeks. ese objective

data are analyzed together with subjective perceptions gathered once (via

a 137-items-study questionnaire and the Maslach Burnout Inventory),

repeatedly (via interviews) or continuously (via ecological momentary

assessments).

Results: e sample consisted of 12 nurses (out of 18; participation rate

66.7 %) aged 22 to 53 years (mean age 34 years). Bioparameters can be

evaluated in 185 complete (66.3 %) and 25 partial shis (9.0 %) out of a

total of 279 shis. Among the rst 6 participants, the total perceived strain

ranged from 7.6 to 15.1 out of 54 possible points in the study question-

naire which suggests a low burden. Within the workplace, the most fre-

quent stressors were stressors related to patients or their relatives, which

were, however, rated as less weighty than stressors related to job structure

and work organization.

Discussion: e acceptance across all participants was high. First data

hint at the methodical and technical eectiveness of the DiPa approach.

However, not all collected data have been analyzed yet. A thorough analy-

sis of particular stressors is currently ongoing and will be presented later.

Conclusion: is innovative study shows the feasibility of using wearable

devices in combination with subjective instruments to measure stress in

palliative care nurses.

Disclosure statement: e project is funded by the Federal State of Mecklen-

burg-Western Pomerania.

660

Patients’ experiences and needs undergoing immune-

checkpoint-inhibitor therapy – A qualitative study

Laura Püschel1; Anne Letsch2; Anne Christin Rahn1; Stefanie Mentrup1

1Institute for Social Medicine and Epidemiology, Nursing Research Unit,

University of Lübeck, Lübeck, Deutschland

2Department of Medicine II, Hematology and Oncology, University Hospital

Schleswig-Holstein, Kiel, Deutschland

Background: People treated for cancer with immune checkpoint inhibi-

tor (ICI) therapies may develop immune-related adverse events (irAEs).

IrAEs can occur at any time with variable clinical presentations and should

therefore be assessed regularly. is qualitative study aimed to explore the

experiences of people with cancer (PwC) undergoing ICI therapy with a

focus on self-management, educational and further needs.

Methods: Semi-structured interviews were conducted with PwC who

received or discontinued ICI therapy. Interviews were audio-recorded,

transcribed verbatim and analyzed thematically.

Results: irteen people (7 women, 6 men) with dierent cancer diag-

noses receiving ICI as mono- or combination therapy participated in the

interviews. ree overarching themes were identied: (1) In a state of

uncertainty: life between hope and fears, (2) continuity as a basis for good

care, (3) spectrum of side eects: impact on self-management and needs.

PwC interviewed, oen found themselves in a state of uncertainty regard-

ing the future course of their illness. In this context, ICI therapy is oen

regarded as the last chance to prolong life. erefore, most of the PwC

prefered passive and fast decision-making. Some interviewees described

that irAEs caused uncertainty and impacted individual information and

support needs as well as self-management. Continuity of care relieved

most PwC interviewed here. In this regard, interviewees described the

benets of a qualied, accessible, and xed contact person.

Discussion: PwC undergoing ICI therapy might benet from a healthcare

professional who supports the treatment trajectory and helps recognizing

irAEs early. Information should be delivered individually according to the

persons’ needs.

Conclusion: is study indicates that uncertainty, irAEs and continuity

of care inuence the needs and self-management of PwC undergoing ICI

therapy. Support programs should consider continuity of care and other

contextual factors of PwC and ICI therapy.

Disclosure Statement: e authors declare the following: Honorare: BMS, Jannsen

Cilag, MSD, Roche, Tesaro; Grünenthal, Astra Zeneca. Novartis, Merck Serono;

Finanzierung wissenschalicher Untersuchungen: Novartis, Tesaro; Andere

nanzielle Beziehungen: Servier; Immaterielle Interessenkonikte: Beisitzerin im

Vorstand der DGP

692

Creating evidence for naturopathic nursing interventions in

oncology – a systematic approach

Regina Stolz1; Nadja Klafke2; Birgit Kröger1; Ursula Boltenhagen3;

Anna Kaltenbach3; Rolf Heine4; Christel Idler5; Monika Layer6; Sara Kohler7;

Marcela Winkler5; Petra Voiss8; Stefanie Joos1; Cornelia Mahler3

1Institute for General Practice and Interprofessional Care, University Hospital

Tuebingen, Tübingen, Deutschland

2Health Services Research and Implementation Science, Department of

General Practice and Health Services Research, University Hospital Heidelberg,

Heidelberg, Deutschland

3Institute of Health Sciences, Department of Nursing Science , University

Hospital Tuebingen, Tübingen, Deutschland

4Anthroposophic Nursing Network, Academy of Anthroposophic Nursing

Professions at the Filderklinik, Filderstadt, Deutschland

5Robert-Bosch-Krankenhaus Stuttgart, Stuttgart, Deutschland

6Department of Integrative Medicine and Department of Nursing Development,

Cantonal Hospital St. Gallen, Schweiz

7Programm director of MAS in Oncological Nursing, Zurich University of Applied

Sciences, Winterthur, Schweiz

8Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte,

Faculty of Medicine, University of Duisburg-Essen, Essen, Deutschland

Background: Nurses working in oncology use a wide range of naturo-

pathic interventions in their daily practice to alleviate symptoms and

improve the quality of life of oncological patients. However, there is no

external evidence for many of these interventions. Due to a lack of sci-

entic studies in the eld, the aim of the project is to develop a standard-

ized procedure to generate evidence on naturopathic interventions, which

enable to draw recommendations for nursing practice.

Methods: e systematic procedure was developed by the working group

(WG) Integrative Nursing in Oncology over a period of four years, in an

iterative process. e process is based on the experience of the expert

panel members in the development of guidelines and/or quality instru-

ments such as practice standards.

Result: e systematic methodological approach consists of three succes-

sive steps where internal and external evidence have been combined: a

scoping review, a structured consensus process (cp) with oncology nurses

to collect and evaluate naturopathic interventions, and a further supple-

mentary literature review based on additional ndings within the cp. e

procedure was successfully carried out for mucositis, insomnia, fatigue,

hand-foot syndrome and chemotherapy-induced poly-neuropathy.

Discussion: e procedure represents a successful theory-practice trans-

fer through structured cooperation between (nursing) scientists and

nursing practitioners. e recommendations for practice developed in

the process can be classied in the AWMF classication between an S1

guideline (informal consensus of an expert group) and an S2e guideline

(evidence-based).

Conclusion: rough the step-by-step synthesis of internal evidence with

the best available external evidence, the evidence base for naturopathic

nursing interventions in oncology can be generated and recommenda-

tions for practice derived.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 183

Oncological Pharmacy

Best-of-Abstract-Vortrag

754

Pharmacist in a Multiprofessional Cancer Care Team in

Germany – Benets Resulting from the Work of an Oncology

Ward Pharmacist

Svenja Dierkes1; Annette Freidank1; Carsten Culmsee2; Roland Radziwill1

1Klinikum Fulda gAG

2Institut für Pharmakologie und Klinische Pharmazie , Philipps-Universität

Marburg, Marburg, Deutschland

Background: Due to high numbers of newly diagnosed cancer patients

and increasing complexity of new chemotherapeutics, there is an increas-

ing demand for better management of patients. Pharmacists are able to

ensure the patient’s safety and quality of life.[1]

e objective of this intervention study is to evaluate the benet of

a pharmacist embedded in a multiprofessional cancer care team on an

oncology ward in Germany.

Methods: e present study is a single-centered, controlled, retrospective,

and prospective intervention study consisting of three dierent phases

P0, P1, and P2. e phases dier regarding the underlying type of data, the

duties of the pharmacy, and the employment of a ward pharmacist (P1 and

P2). In the rst phase (P0), two clinical pharmacists independently identi-

ed all medication errors (MEs) which they detected from archived med-

ical le. For the second and third phase, an electronic patient record has

been implemented and the ward pharmacist determined, documented,

and solved MEs as part of her daily work. In all phases, the classication

as ME was set only aer conrmation by an oncologist to ensure clinical

relevance.

Result: e three phases with 52, 46, 50 patients, respectively, were com-

parable regarding the baseline characteristics. For better comparability the

MEs refer to the number of medication lines which comply with one drug

per day. e statistical analysis showed a signicant reduction of clini-

cally relevant MEs (P0: 33 MEs/ 100 medication lines vs. P1: 7 MEs/ 100

medication lines vs. P2: 2 MEs/ 100 medication lines; (p < 0,001)) for the

three phases.

Conclusion: e implementation of a ward pharmacist had a signicant

impact on the reduction of MEs consequently increasing the patient’s

safety.

Indication of source

1 E. M Segal, et al . J Oncol Pharm Pract 2019

Disclosure Statement: e authors declare no conict of interest.

Poster

655

Evaluation of knowledge, usage behavior and user

expectations of an oral anticancer drug database and

information system – qualitative cognitive pretesting with

dierent types of target groups

Sahra Kießig1; Tessa Richter1; Ste Chalas1; Klara Gren2;

Holger Muehlan2; Franziska Ockert-Schön3; Michael Höckel4;

Christoph Ritter1

1Institut für Pharmazie, Universität Greifswald, Klinische Pharmazie, Greifswald,

Deutschland

2Institut für Psychologie, Universität Greifswald, Gesundheit & Prävention,

Greifswald, Deutschland

3Deutsche Gesellschaft für Onkologische Pharmazie, Projektmanagement Oralia

Initiative, Hamburg, Deutschland

4Gesundheit Nordhessen Holding AG, Zentralbereich Apotheke, Kassel,

Deutschland

Background: e use of oral anticancer drugs requires close attendance

by health care professionals. Information systems exist that are intended

to support patient care. e aim of this study is to evaluate knowledge,

usage behavior and expectation of the Oralia oral anticancer drug data-

base among members of the German Society of Oncological Pharmacy

(DGOP) with a focus on interdisciplinary exchange.

Methods: A questionnaire was developed on knowledge, usage behavior

and expectations of the Oralia database. Pretesting was conducted among

three groups of potential users. e survey will be sent to all members of

the DGOP. e answers will be analyzed using descriptive statistics.

Result: Pretesting was conducted with pharmacy students (n=3), mem-

bers who do not know the database (n=3), members who know but do not

use the database (n=3), and recent and current users (n=6). Main issues

were unspecic descriptions of processes when using the database, illog-

ical order of possible answers, and inconsistent wording. Some aspects

were missing such as educational needs. e questionnaire was adapted

accordingly. All participants agreed with content and length.

Discussion: Subsequent adaptation of the questionnaire improved read-

ability and comprehensibility with no relevant extension of the question-

naire. e nal questionnaire contains ve sections that address (I) usage

conditions, (II) expectations and demands on the database, (III) expecta-

tions and demands on the patient management tool of the database, (IV)

improvements and future use, and (V) demographic data. For members

that do not know the database or know the database but do not use it the

questionnaire consists of sections I, V and selected questions from section

II. Previous and current users will receive the complete questionnaire.

Conclusion: Results of the survey will be presented during the meeting.

Results of this evaluation will provide better insights into and improve the

usage of the Oralia database and ultimately patient care.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts184

Other Topics

Poster

171

Vaccination status of oncological patients under treatment;

preliminary baseline data of the Easy Vaccination in Oncology

(EVO) Study

Katrin Trostdorf1; Nicola Delmastro2; Arne Gerrit Salomon3;

Maria Duran Cortes2; Mark Reinwald4; Christian Scholz5;

Ernst Späth-Schwalbe6; Veit Mannsmann7; Maike de Wit2;

Til Ramon Kiderlen1

1Vivantes Klinikum Neukölln, Klinik für Innere Medizin - Hämatologie, Onkologie

und Palliativmedizin, Berlin, Deutschland

2Vivantes Klinikum Neukölln, Innere Medizin - Kardiologie, Angiologie,

Nephrologie und konservative Intensivmedizin, Berlin, Deutschland

3Vivantes Klinikum Neukölln, Klinik für Innere Medizin - Pneumologie und

Infektiologie, Berlin, Deutschland

4Medizinische Hochschule Brandenburg - Theodor Fontane, Innere Medizin -

Klinik für Hämatologie und Onkologie, Brandenburg, Deutschland

5Vivantes Klinikum Am Urban, Klinik für Innere Medizin - Hämatologie und

Onkologie, Berlin, Deutschland

6Vivantes Klinikum Spandau, Klinik für Innere Medizin - Hämatologie, Onkologie

und Palliativmedizin, Berlin, Deutschland

7Vivantes Humboldt-Klinikum, Klinik für Innere Medizin - Onkologie, Berlin,

Deutschland

Introduction: e German Standing Committee on Vaccination

(STIKO) recommends vaccinations for oncological patients

(Bundesgesundheitsblatt 2020). ere is no public data on vaccina-

tion rates for these patients, but health insurance data suggest low rates

(Schmedt et al. 2017).

Methods: e EVO study was an interventional study to increase vaccina-

tion rates in oncology. For this abstract we analyzed the vaccination status

of oncological patients under treatment of the baseline, hence non-inter-

ventional, population. Data collection was conducted in 4 Medical Care

Centers (MCC) in Berlin, Germany (Jan - Nov 2020). All eligible patients

were asked to present their vaccination card. Only up-to-date vaccinations

were counted as valid. Missing vaccination cards counted as unvaccinated.

Results: Of 448 contacted patients, 242 (54,0%) were included; 151

(33,7%) did not respond. 55 (12,3%) patients were excluded. 177 (73,1%)

included patients provided their vaccination card; 65 (26,9%) could not

make a vaccination card available.

We found moderate rates for vaccinations against tetanus (51,2%), diph-

theria (48,8%) and pertussis (43,4%). Hepatitis B vaccination rates were

signicantly lower (15,7%) as were the rates for inuenza, with 25,2%.

Vaccination rates against pneumococci were even lower: 5,4% received

sequential vaccination with Prevenar13® and Pneumovaxx23®, 7,9% were

vaccinated with Prevenar13® only and 21,9% with Pneumovaxx23® only.

Similarly low vaccination rates were documented for meningococci, with

3,7% (Typ C) and herpes zoster, with 2,9%.

Conclusion: Our data show unsatisfactory low vaccination rates for

oncological patients. Dierent reasons are suspected to contribute to this

outcome, including lack of knowledge regarding vaccination by the oncol-

ogist and uncertainties regarding the underlying condition by the vacci-

nating physicians (Orange et al. 2012). ere is an urgent need to improve

communication between oncologists and family doctors, to target these

shortcomings.

Disclosure Statement: e authors declare no conict of interest.

198

A Multidisziplinary Analysis of Informed Consent Forms of

Clinical Trials in Hematology

Susann Schulze1; Nadja Jäkel2; Christin Naumann2; Marion Hackl1;

Sandra Ehlert1; Marcus Bauer3; Ute Berndt4; Petra Büchner-Steudel5;

Timo Faltus6; Katharina Jenner1; Kerstin Junghans7; Eva Kantelhardt4;

Christiane Ludwig5; Rose C.K. Moritz8; Adrienne Neustadt1; Andre Nowak9;

Bastian Ignaz Preissler1; Fana-Lamielle Samatin1; Jan Schildmann9;

Heike Schmidt10; Sandra Schönburg11; Stefanie Stegmann5; Janine Stingl1;

Hans Zillmann12; Haifa Kathrin Al-Ali1

1University Hospital Halle, Krukenberg Cancer Center Halle (Saale), Halle (Saale),

Deutschland

2University Hospital Halle, Department of Hematology/ Oncology, Deutschland

3Institute of Pathology, University Hospital Halle, Halle (Saale), Deutschland

4University Hospital Halle, University Clinic and Outpatient Clinic for

Gynecology, Halle (Saale), Deutschland

5University Hospital Halle, Department of Internal Medicine Gastroenterology/

Pneumology, Halle (Saale), Deutschland

6Faculty of Law and Economic Sciences, Martin-Luther-University Halle-

Wittenberg, Halle (Saale), Deutschland

7Martin-Luther-University Halle-Wittenberg, Faculty of Law and Economic

Sciences, Halle (Saale), Deutschland

8University Hospital Halle, University Clinic and Outpatient Clinic for

Dermatology and Venereology, Halle (Saale), Deutschland

9Institute for History and Ethics of Medicine, Interdisciplinary Center for Health

Sciences, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle

(Saale), Deutschland

10University Hospital Halle, University Clinic and Outpatient Clinic for

Radiotherapy, Halle (Saale), Deutschland

11University Hospital Halle, University Clinic and Outpatient Clinic for Urology,

Halle (Saale), Deutschland

12Interdisciplinary Centre for Medicine, Ethics, Law, Martin-Luther-University

Halle-Wittenberg, Halle (Saale), Deutschland

Introduction: Clinical trials (CT) are regulated by Good Clinical Practice

(GCP) (Directive 2001/20/EC). For an independent patient (pt) deci-

sion-making, the informed consent form (ICF) is essential. We evaluated

ICFs from pt, healthcare professional, ethical, and legal perspectives.

Methods: ICFs of 38 hematologic CTs conducted at the University

Hospital Halle from 2005 and 2020 were included. Each sponsor- and

year-blinded ICF was independently evaluated by pts, physicians (Phy),

psycho-oncologists (Psy), legal professionals (Law), and ethicists (Eth)

based on a catalogue of 62 questions in 6 categories (Cat) [readability/

comprehensibility (A), CT details (B), benets/risks (C), personal data

protection (D), self-determined decision of pts (E), declaration of con-

sent (F)]. Rating options were optimal, unavailable/too-little, too-much,

and "cannot answer". Finally, each ICF was graded from 1 (very good)

to 6 (unsatisfactory). Each panelist evaluated a median of 5 ICFs with a

median length of 27 pages per ICF.

Results: From the 12799 possible answers, 3% were missing. Overall, only

31% (19/62) of questions were rated as optimal by >75%. Across all Cat

and in particular in Cat B and C, healthcare professionals rated similarly

or more critically compared to pts, Eth or Law. e majority of panelists

agreed that ICFs missed gures and summaries in Cat A. Rating discrep-

ancies were evident in Cat B between pts and Law/Eth [optimal 74% and

72% vs. too- little 56% and 51% respectively]. Cat C with 59% received

the lowest optimal rating mainly due to critical ratings by healthcare pro-

fessionals. Unexpectedly, 82% of pts and Law rated Cat D as optimal vs.

only 65% by Eth. Cat E was the only Cat were pts rated lower than other

panelists. Pts criticized the lack of an individual language and space for

remarks. Cat F was unproblematic with an optimal rating of 84%. Overall,

ICFs received a median grade of 2 (range 1-6). Psy were most judgmental

with a median grade of 3.

Conclusions: Our data show that although ICFs full the GCP require-

ments, there is substantial room for improvement in the interest of pts.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 185

272

Prevalence of idiopathic multicentric Morbus Castleman in

patients suering from cervical lymphadenopathy

Michael Krokenberger1; Kristina Schwamborn2; Ulrich Straßen1

1Klinikum rechts der Isar der Technischen Universität München,

Otorhinolaryngology / Head and Neck Surgery, München, Deutschland

2Klinikum rechts der Isar der Technischen Universität München, Institute of

Pathology, München, Deutschland

Background: Idiopathic multicentric Morbus Castleman (iMCD) is a

very rare disease with a broad spectrum of symptoms and a complex his-

topathological diagnosis. An expert meeting in 2017 dened new criteria

for the diagnosis for iMCD. It is estimated that in the US there are about

2-20 cases per one million patient years. Estimations for the German pop-

ulation do not exist yet. As lymphadenopathy oen occurs primarily in

the head and neck region patients are frequently referred to the otorhi-

nolaryngology department for further dierential diagnosis and biopsy.

Methods: e aim of this retrospective cohort study is to determine the

prevalence of iMCD in patients, who underwent a lymph node removal

in our clinic between 2010 and 2020. erefore, epidemiologic, laboratory

and clinical data was analysed descriptively while diagnosis of mono- and

multicentric M. Castleman disease were made utilizing the international

diagnostic criteria proposed by Fajgenbaum et al (2017).

Result: 714 patients suering of cervical lymphadenopathy were included

into the study. In 75 patients matching the clinical criteria for the diag-

nosis of iMCD histopathologic samples were re-analysed by a histopa-

thologist. 14 cases (1,9%) matched the histopathological major criterion

dened by Fajgenbaum et al, 2 cases (0,3%) matched for both major and

minimum required minor criteria.

Discussion: e new criteria from Fajgenbaum et al. oer an objective

tool for the diagnosis of iMCD. Even if the histopathological major crite-

rion oen ts for the extirpated lymph nodes, ≥ 2 enlarged lymph node

stations and complementary minor criteria were oen missing for the

nal diagnosis.

Conclusion: In our population aer utilization of the new criteria 1,9%

of patients could be diagnosed with monocentric and 0,3% could be diag-

nosed with iMCD in contrast to 0,1% respectively beforehand. Although

incidence and prevalence of iMCD are low, clinicians should keep in mind

this dierential diagnosis as eective therapies are available.

Disclosure Statement: e authors declare no conict of interest.

418

Inuencing factors for routine implementation of shared

decision-making in oncology: process evaluation of a stepped

wedge cluster-randomized trial

Anja Lindig; Pola Hahlweg; Wiebke Frerichs; Hannah Cords;

Jördis Zill; Isabelle Scholl

1Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum

Hamburg-Eppendorf, Hamburg, Deutschland

Background: Shared decision-making (SDM) is highly relevant in oncol-

ogy but rarely implemented in routine care. e outcome evaluation of an

implementation program to foster SDM in routine cancer care1 did not

nd an eect on SDM implementation from patients’ view. e aim of

this study was to analyze inuencing factors on SDM implementation in

routine cancer care.

Methods: We conducted a qualitative process evaluation of a stepped

wedge SDM implementation trial. Data included interviews with clini-

cal stakeholders, eld notes of the study team and minutes of meetings

with clinical collaboration partners. Data were analyzed via inductive

and deductive qualitative content analysis on basis of the Consolidated

Framework for Implementation Research (CFIR)2.

Result: Transcripts of 107 interviews, 304 pages of eld notes and 125

pages of meeting minutes were analyzed. Major inuencing factors on

SDM implementation were found on all levels of the CFIR: a) four on

the individual level (e.g., perceived personal relevance, individual moti-

vation to change), b) eleven on the organizational level (e.g., leadership

engagement, resources), c) two on the level of the health care system (e.g.

culture of healthcare delivery), d) eight regarding characteristics of the

intervention (e.g., translation into clinical practice, relative advantage),

and e) three regarding the implementation process (e.g., integration into

existing structures). We found strong correlations between several inu-

encing factors within and between levels.

Discussion: is comprehensive process evaluation provides approaches

for the interpretation of the outcome evaluation of the SDM implemen-

tation study. Future studies should investigate which of these factors are

predictors for implementation success.

Conclusion: e identied inuencing factors can be used for planning,

conducting and evaluating future SDM implementation studies.

References:

1 Scholl* I, Hahlweg* P, Lindig A, et al. (2021) Implementation Science.

16(1):106.

2 Damschroder LJ, Aron DC, Keith RE, et al. (2009) Implementation Science.

4:50.

Disclosure Statement: e authors declare no conict of interest.

467

What’s its worth? “Likes” as surrogate marker for interest

indigital medical education

Judith Büntzel; Julia Felicitas Leni König; Rebecca Wurm-Kuczera

Georg- August-Universität, Universitätsmedizin, Klinik für Hämatologie und

Onkologie, Göttingen, Deutschland

Background: Instagram is a novel tool in medical education and “likes”

are oen used as surrogate markers to measure interest. However, “likes”

have not been validated so far. We launched an educational Instagram

account teaching hematology and oncology and compared the numbers

of “likes” with an independent survey measuring the interest among the

participating students.

Methods: e Instagram account “ilearnonco2021” was generated and

teaching material was uploaded twice a day. Students were invited to

subscribe via e-mail and online announcements. “Likes” per post were

assessed. Once the teaching module was concluded, we launched an eval-

uation assessing students’ interest in posts of the category “mnemonics”

and “clinical diagnostics” (blood smear, CT images) on a ve-point Likert

scale. Mann-Whitney U Testing was used to compare “likes” to the results

of our survey.

Result: 49 of 124 students enrolled in the teaching module subscribed.

Overall, we garnered 0.02 likes per post and follower number. e highest

“likes per post and follower number” (LPF) were observed in the posting

categories “mnemonics” and “clinical diagnostics” with 0.034 and 0.037

LPF respectively, indicating an increased interest. We assessed the stu-

dents’ interest in a separate evaluation at the end of the teaching module.

Comparing trends in interest between the two tools- “LPF” and the sur-

vey results, Mann-Whitney U testing revealed no signicant dierence

between both tools, indicating similar trends in students’ interest.

Discussion: So far, “likes” have been used as tool in digital research as

surrogate marker for interest. To our knowledge, we are the rst trying to

evaluate, whether “likes” are a suitable tool to estimate trends in interest

in medical education.

Conclusion: “Likes per post and follower” are suitable to estimate trends

in interest. e observed trends should be validated with a second tool,

e.g. an independent survey to conrm the ndings.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts186

502

Genomic HLA homozygosity is frequent in esophago-gastric

adenocarcinoma and related to low immunogenicity

María García-Márquez1; Martin Thelen1; Eugen Bauer2; Jonas Lehmann1;

Diandra Keller3; Birgit Gathof2; Lukas Maas4; Julie George3;

Christiane Bruns1; Alexander Quaas5; Michael von Bergwelt-Baildon6;

Martin Peifer7; Hans Schlößer1

1Uniklinik Köln, Zentrum für Molekulare Medizin Köln, Klinik und Poliklinik für

Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie, Köln, Deutschland

2Uniklinik Köln, Transfusionsmedizin, Köln, Deutschland

3Uniklinik Köln, Clinics Head and Neck Surgery, Department of Translational

Genomics, Köln, Deutschland

4Uniklinik Köln, Department of Translational Genomics, Köln, Deutschland

5Uniklinik Köln, Pathologie, Köln, Deutschland

6Ludwig Maximilians University, Department of Medicine III, München,

Deutschland

7Uniklinik Köln, Computational Cancer Genomics , Department of Translational

Genomics, Köln, Deutschland

Background: e HLA-genotype of a person denes the repertoire of

peptides that can be presented to T cells. We aimed to determine if HLA-I

homozygosity could translate in a smaller repertoire of tumour neoanti-

gens potentially predisposing such individuals with a disadvantage to ght

a nascent tumour.

Methods: High-resolution HLA-genotyping combined with (1) the 10

most important cancer testis antigens (CTAs) in EGA (n=80) and (2) non-

synonymous mutations called from WES data (n=38) was used to predict

high and moderate anity binders with the “Immune Epitope Data Base”

(iedb.org). RNA-extraction and gene expression proling were performed

using NanoString technology.

Result: Frequency of HLA homozygosity in EGA patients (n=80, 35%)

was unexpectedly higher than that in the control population (n=7.615,

19%). Comparison of both cohorts revealed an odds ratio for homozy-

gosity of at least one allele of 2.28 (p<0.001). Analysis of the amount of

tumour-specic high and moderate-anity binders conrmed a reduced

repertoire of potentially immunogenic peptides in homozygous EGA

patients. In line with this observation, increased levels of CTA expression

in homozygous compared to heterozygous patients were found. Aer

articial modication of the genotype of homozygous patients to a het-

erozygous genotype, the set of predicted good-binding peptides was com-

parable to the heterozygous cohort.

Discussion: Our results show a high frequency of HLA-I homozygos-

ity among EGA patients compared to healthy donors. Additionally, we

show that dierences in the number of available HLA-I molecules in a

given individual can present major challenges to eective antitumor T cell

responses that may facilitate immune evasion and may reect an increased

cancer risk for these patients.

Conclusion: Together with previous reports demonstrating reduced

survival aer checkpoint therapy, our study suggests consideration of

germ-line HLA-homozygosity for the design and interpretation of immu-

notherapeutic trials.

Disclosure Statement: e authors declare the following:

MvBB: Honoraria for advisory boards, for invited talks from BMS and nancial

support for research projects from Astellas, Roche and MSD; H.S.: Funding for

clinical Research by Astra Zeneca. Honoraria for advisory board from BMS; e

remaining authors declare no competing nancial interests

519

Structural and processual characteristics of multidisciplinary

tumor conferences from the physicians’ perspective

Kerstin Hermes-Moll1; Ulrike Mönnigho1; Thomas Walawgo1;

Vitali Heidt1; Jochen Heymanns2; Mathias Bertram3

1Wissenschaftliches Institut der Niedergelassenen Hämatologen und

Onkologen (WINHO) GmbH, Köln, Deutschland,

2Praxis für Hämatologie und Onkologie, Koblenz, Deutschland,

3Onkologie Partner, Praxis am Albertinen Krankenhaus, Hamburg, Deutschland

Background: Multidisciplinary tumor conferences (MTC) are an import-

ant and resource-intensive part of cancer care. Yet, there is a lack of knowl-

edge about structures and processes of MTC in Germany, esp. outside of

certied centers. Further, there is little information about potential quality

issues and measures to assure and improve the quality of MTC. is study

was supported by the Zentralinstitut für die kassenärztliche Versorgung in

der Bundesrepublik Deutschland (Zi).

Methods: An online survey was conducted from September 2021 until

January 2022. e questionnaire addressed structures, processes, and

quality of MTC. Physicians who treat cancer patients were invited to

participate via several professional organizations, e-mails, yers, social

media, and press. Data were collected anonymously and analyzed using

SPSS.

Result: Data from 612 respondents were included in the analysis.

Regarding the last MTC they attended, 83% stated that this MTC was

conducted by a certied center. MTC were held in presence in half of the

cases (51%), 30% in hybrid, and 19% purely virtual. e median value

for the duration of the MTC was 45-60 minutes, 11-15 for the number of

patients discussed, and 6-10 for the number of participants. However, the

range is large in each case. Concerning processual characteristics, signi-

cant dierences between MTC in certied and non-certied centers could

be identied, among others.

Discussion: e survey results show a great diversity regarding structural

characteristics of MTC. But there are also clear dierences with regard to

process-relevant factors, i.e. clearly dened guidelines and rules.

Conclusion: e results of this online survey provide a unique insight

into the landscape of MTC in Germany. Based on the results, critical

aspects and needs for further improvement of MTC can be identied and

addressed to optimize cancer care and time spent by physicians.

Disclosure Statement: e authors declare no conict of interest.

540

Patient seminars in oncology - online vs. presence: Has the

pandemic changed everything? Experiences after one year

of online events and results of a patient survey conducted by

CIO Cologne in July 2021

Sabine Treppner1

1Uniklinik Köln, Centrum für Integrierte Onkologie, Köln, Deutschland

Background: Aer the outbreak of the COVID-19 pandemic in spring

2020, it was no longer possible to hold face-to-face seminars with our

cancer patients. Nevertheless, there was an ongoing need for information

among the patients – in particular related to cancer and COVID-19.

Methods: Together with the patient representative from the board of our

cancer center, the Center for Integrated Oncology (CIO) at the University

Hospital Cologne, we discussed how a patient-oriented online format

could be designed. According to the principle “Monday is patient day”

a weekly, one-hour, moderated series of events was elaborated, for which

participants register only once and which alternates between entity-

specic and general topics like immunotherapy, nutrition, cancer and

sports. A key element of this new format was its interactive character

with very lively discussions. In additions, all events were available for the

patients as recordings.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 187

Result: A total of 41 events were held from August 2020 to July 2021. A total

of 1,298 people took part (max 95 /min 10) - this corresponds to an average

of 31.6 participants per event – with arising trend. e total of 32 recordings

have so far been accessed by a total of 1,598 people (max 140 / min 8) - this

corresponds to an average of 50 viewers per recording. (As of 8/30/2021)

Asked about their preference in the future, only 7% of 151 registered

online participants prefer a face-to-face event - 63% voted for online. 31%

would decide on a case-by-case basis.

Discussion: It was unclear, particularly among older oncology patients,

whether they would accept an online format well. ese concerns were

completely dispelled by both, the number of participants and the feed-

back from the survey. Compared to the face-to-face events before the

pandemic, participation was also signicantly increased through online.

Conclusion: e pandemic can be seen as a catalyst for a switch in infor-

mation sessions for oncology patients to online formats.

Disclosure Statement: e author declares no conict of interest.

609

Vascularsurgical aspects in oncosurgery of the retroperitoneal

space – representative case series

Frank Meyer1; Zuhir Halloul2

1Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-

Guericke University at Magdeburg with University Hospital, Magdeburg,

Deutschland,

2Division of Vascular Surgery, Dept. of General, Abdominal, Vascular and

Transplant Surgery, Otto-von-Guericke University at Magdeburg with University

Hospital, Magdeburg, Deutschland

Aim: Exemplary demonstration of vascular alterations incl. its recon-

structive options as part of retroperitoneal tumor(Tu) resections out of

the broad oncosurgical prole to achieve R0 resection status.

Method: Representative case reports showing technical feasibility & early

postop. outcome.

Results: 1) Preparative freeing of the Tu adherence of a retroperitoneal

so tissue sarcoma from the aorta near the sup. mesenteric artery (SMA)

& coeliac trunc incl. “le resection“ of the pancreas (+splenectomy, le

nephrectomy)/partial gastric/diaphragmatic resection (+thoracic drain-

age & suture of the intestine).

2) Multivisceral Tu resection of a retroperitoneal so tissue sarcoma, with

resection o he coeliac trunc & reconstruction of the hepatic artery using

venous interponate from the SMA.

3) Pancreatic head resection in a 45-year old patient with arterial supple-

mentation of the liver out of the SMA (hepatomesenteric trunc) only rec-

ognized aer ligation & surgical sectioning of the gastroduodenal artery

→ reconstruction with mesentericohepatic venous bypass.

4) Tu exstirpation of a right retroperitoneal neurinoma with adherence

to inferior vena cava, common iliac artery & psoas muscle w/o required

vascular reconstruction.

5) Tu resection of a primary inferior-vena-cava sarcoma comprising

vena-cava resection incl. the mouths of renal veins & reconstruction with

ringed PTFE prosthesis (Ø: 20 mm) reimplanting the renal veins.

6) Intraop. lesion of the SMA in Tu resection of a recurrent GIST at the

mesenteric root (intraperitoneal adhesions aer former peritonitis & sev-

eral laparotomies,recurrent liver metastases within segment 3, 4b, 5/8 &

ovarian tumor at both sides) reconstructed with venous patch plasty.

Conclusion: Vascular reconstructions partially necessary for a better

prognosis in interdisciplinary cases of abdominal & vascular surgery

require clinical & vascularsurgical expertise in reconstructions as well as

an interdisciplinary collaboration of interventional radiology & intensive

care in the perioperative management.

Disclosure Statement: e authors declare no conict of interest.

631

Technology acceptance of oncology patients with exercise

therapy needs to telemedicine-sports science services

Dominic Schmidt; Nora Zoth; Freerk T. Baumann

AG Onkologische Bewegungsmedizin, Uniklinik Köln, Centrum für Integrierte

Onkologie (CIO), Köln, Deutschland

Background: eHealth solutions promise great potential to provide can-

cer patients with individualized and scientically based exercise services

independent of time and location. ere is too little data on the accep-

tance of oncology patients for such products. erefore, this study investi-

gated cancer patients’ acceptance of telemedicine-sports science products.

Methods: 63 patients were shown a mock-up of a web browser por-

tal based on the concept of oncology exercise and movement therapy

(Onkologische Trainings- und Bewegungstherapie - OTT). ey then

completed an online questionnaire based on the technology acceptance

model. e acceptance of the respondents was measured by the item

"intention to use" (5-point Likert scale).

Result: e acceptance of the patients proved to be high. For the three

dierent functions of the product presented, the intention to use ranged

from 3.97 to 4.02. No age-related signicant dierences were found for the

mean scores (cut-o value 60 years).

Discussion: Overall, as suspected, a high level of acceptance was found.

Contrary to expectations, persons ≥ 60 years of age did not have a lower

expression in the item “Perceived ease of use”. e sample was small, so

this study is considered a pilot.

Conclusion: Probably, this online survey was thematically the rst of its

kind in Germany. It shows a positive attitude of the patients to the outlined

product. Further studies should follow. On the one hand, the question

arises as to which other variables inuence the intention to use (possibly

e.g., eHealth literacy or previous sports experience). On the other hand,

patients should be involved in the development of digital oerings from

the user perspective.

Disclosure Statement: e authors declare no conict of interest.

702

Mobile assessment of adverse events and other patient

reported outcomes (PROs) to guideinpatientcancer care:

athree-arm randomized controlled feasibility study

Hanna Salm1,2; Leopold Hentschel3; Michael Kramer4; Daniel Pink1,2;

Martin Eichler3,4; Markus K. Schuler4,5

1Department of Internal Medicine C, University Hospital Greifswald, Greifswald,

Deutschland

2Helios Hospital Bad Saarow, Bad Saarow, Deutschland

3University Cancer Center (NCT/UCC), University Hospital Carl Gustav Carus,

Technical University Dresden , Dresden, Deutschland

4Department of Internal Medicine I, University Hospital Carl Gustav Carus,

Technical University Dresden, Dresden, Deutschland

5Onkologischer Schwerpunkt am Oskar-Helene-Heim, Berlin, Deutschland

Background: e objectives of this study were to implement an electronic

assessment of patient reported outcomes (PROs) in inpatient cancer care

and test its feasibility. e eect of the mobile tool on symptom burden

and patients’ satisfaction with care was explored.

Methods: e study is an interventional, three-arm and multicenter inpa-

tient trial. A self-administered questionnaire consisting of several aspects

of quality of life using validated PRO-measures was applied and completed

at admission, one week aer and at discharge. Group A (intervention arm)

and B completed the questionnaires on a tablet computer, while group C

(control) completed the questionnaire on paper. Additional to the mere

of electronic patient reported outcome (ePRO) assessment, results from

group A were presented graphically to the treating physicians. A feasibility

questionnaire was administered to arm A and B.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts188

Result: N=185 patients were recruited in oncology wards. e majority

preferred the electronic version and believed the intervention had the

potential to improve care as well as had a positive impact on their treat-

ment. Unexpectedly, scores for satisfaction with care were signicantly

lower (p 0.047) in the intervention group (mean 3.55) versus the control

group (mean 3.77). Symptom burden did not signicantly change during

hospitalization.

Conclusion: ere is limited data available concerning ePRO assessment

in inpatient units. Our results indicate that the intervention is feasible.

We can therefore contribute to foster sustainable integration of ePRO in

the clinical routine. e results are counterintuitive but could possibly be

inuenced by missing physician compliance. ePRO success relies on the

investment of both sta and patients. Future work is needed to further

explore ePRO implementation in inpatient cancer care.

Disclosure Statement: e authors declare no conict of interest.

773

Inuence of the corona pandemic in exercise behavior,

quality of Life, anxiety and depression symptoms in adult

German cancer patients – an online survey:

Juliane Schenk1; Annika Klein1; Timo Niels2; Freerk Baumann2

1Institut für Kreislauorschung und Sportmedizin , Deutsche Sporthochschule

Köln, Köln, Deutschland

2CIO - Centrum für Integrierte Onkologie Uniklinik Köln, AG Onkologische

Bewegungsmedizin, Köln, Deutschland

Background: Covid-19 led to signicant restrictions in the daily life

for the German population. e aim of this study was to assess how the

corona pandemic impacted on physical activity (PA) behavior, quality of

life (QoL) as well as anxiety and depression symptoms of cancer patients.

Methods: Between May and July 2020, an online survey was conducted

for adult cancer patients in Germany, with access to organized exercise

programs. e questionnaire consisted of a cancer history, questions

about PA and exercise behavior before and during the pandemic, as

well as the standardized questionnaires EORTC C-30, HADS and FFKA

questionnaires.

Result: 117 subjects completed the survey. Exercise behavior was sig-

nicantly reduced during the pandemic compared to before (p = 0.004).

70.1% of the subjects stated that they are exercising less than before the

pandemic. With an average score of 58.12 within the global QoL scale,

patients met the matched reference values (61.4). e social function

scale achieved the lowest score (57,1. vs. reference data: 75,0) and physical

function the highest (74.2 vs. reference data: 76,7). On the symptomatic

scales, fatigue scale showed the highest symptom burden (48,24 vs. refer-

ence data: 34,6). 70.9% of the included patients stated that the restriction

of social contacts due to the pandemic had an impact on their QoL. e

mean HADS score was 10.62 points with 33.3% of the subjects exceeding

the cut-o value of ≥ 13.

Conclusion: PA decreased signicantly during the pandemic. QoL is

reduced compared to pre-pandemic EORTC reference data, with the

social function being most impaired. Regarding the development of

mental disorders, the sample can be classied as endangered. e use of

screenings for mental illnesses should be given greater consideration in

oncological care. Further studies are needed to assess the longer-term

impact of the corona pandemic on exercise behavior and psychosocial

eects in cancer patients.

Disclosure Statement: e authors declare no conict of interest.

816

Allocating resources in cancer care during pandemic.

Findings from a qualitative interview study with oncologists

and ethical analysis

Sabine Sommerlatte1; Anna-Lena Kraeft2; Celine Lugnier2; Eleni Kourti2;

Anke Reinacher-Schick2; Jan Schildmann1

1Institute for History and Ethics of Medicine, Martin Luther University Halle-

Wittenberg, Halle (Saale), Deutschland

2Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital,

Ruhr University Bochum, Bochum, Deutschland

Background: Allocation of resources towards the treatment of patients

with Sars-CoV-2 may aect the quality of care of cancer patients. Medical

societies have issued statements on priority setting in cancer care in the

wake of the Sars-CoV-2 outbreak (1). However, there is a lack of empirical

data on how resources are prioritized and which criteria these decisions

are mainly based on by those involved in decision making.

Methods: 15 semi-structured interviews were conducted with oncologists

in Germany between February and July 2021. Transcripts are analysed

following principles of qualitative content analysis based on Kuckartz (2).

Result: According to preliminary analysis three main topics emerge: 1.

Experiences with scarcity regarding specic diagnostic procedures and

treatment 2. Eects of priority setting on coping and psycho-social sup-

port 3. Criteria for priority setting and decisions on deviations of stan-

dards of care. Reported criteria could be further distinguished into three

subcategories: a) criteria related to the health condition of the patient (e.g.

diagnosis, urgency of the procedure), b) pandemic-related organizational

issues (e.g. hygiene requirements), c) systemic aspects not related to the

pandemic (e.g. priorisation of well-paid interventions).

Discussion: Our data indicate that pandemic-related organizational issues

inuenced priority setting, which needs to be addressed. Furthermore,

interviewees agree in posteriorising palliative and follow up care, which

needs to be discussed regarding possible negative side eects.

Conclusion: Data will be interpreted focussing on the possible contribu-

tion to an informed guidance for priority setting regarding cancer care in

times of pandemic.

Indication of source:

1 Marron, JM et al. Ethics and Resource Scarcity: ASCO Recommendations for

the Oncology Community During the COVID-19 Pandemic. J Clin Oncol.

2020 Jul 1;38(19):2201-2205. doi:10.1200/JCO.20.00960.

2 Kuckartz, U. (2018). Qualitative Inhaltsanalyse. Methoden, Praxis, Computer-

unterstützung (4. Auage). Beltz Juventa.

Disclosure Statement: e authors declare no conict of interest.

835

Impact of the COVID-19 pandemic on cancer care services.

Qualitative interviews with health care users

Tugba Aksakal1; Yüce Yılmaz-Aslan1,2,3; Patrick Brzoska1

1Universität Witten/Herdecke, Fakultät für Gesundheit, Department für

Humanmedizin, Lehrstuhl für Versorgungsforschung, Witten, Deutschland

2Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG3

Epidemiologie und International Public Health, Bielefeld, Deutschland

3Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG6

Versorgungsforschung und Pegewissenschaft, Bielefeld, Deutschland

Background: Due to restrictions caused by COVID-19 and concerns

about contracting SARS-CoV-2, health care users avoided the health care

system, were less likely to have cancer screenings and delayed consulting a

doctor even if they had symptoms. As a result, more advanced cancers are

diagnosed, which are more dicult to treat. ere were also limitations in

ongoing cancer treatments. e aim of the study was to a) identify strate-

gies used in cancer care and prevention settings to mitigate the pandemic

and b) to assess the perceptions of these strategies by care users.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 189

Methods: In autumn 2021, 12 qualitative interviews were conducted with

health care users, including 8 cancer patients and 2 people each who did

or did not have screenings during the rst peak phase of the pandemic.

e interviews were analysed using content analysis.

Result: Reasons given by respondents for attending screening was a fam-

ily history of or having already survived cancer. Although they were con-

cerned about contracting SARS-CoV-2 during screening, they considered

the uncertainty about a potential cancer more worrying. Non-participants

cited concerns about infection and fear of a COVID-19 test as reasons for

non-participation, despite some having a family history of cancer. Cancer

patients perceived therapies carried out in isolation without relatives or

fellow patients as stressful. Compared to cancer, an infection with SARS-

CoV-2 was perceived as less threatening.

Discussion: Health care users and cancer patients, some of whom belong

to a risk group, are partly unaware of the risks associated with COVID-19

and missed cancer screenings. e low risk awareness was also reected in

the comparatively low vaccination rate of the sample, which could not be

attributed to medical reasons. Emotional support for cancer patients has

suered since the outbreak of the pandemic.

Conclusion: e risk awareness of health care users must be increased.

Psychosocial support for cancer patients must be ensured, especially in

times of crisis.

Disclosure Statement: e authors declare no conict of interest.

844

Caught in Speechlessness: First insights in patients with

oncology diseases

Thilo Dietz1; Vera Schiewer1; Sally Tavenrath1; Hildegard Labouvie1;

Michael Kusch1

1Klinik I für Innere Medizin, Universitätsklinikum Köln, Köln, Deutschland

Background: Speechlessness is a new and so far barely investigated eld

of research in psychology. e Cologne Questionnaire on Speechlessness

(KFS) [2] is the rst survey instrument that measures speechlessness

due to diculties in emotional perception and processing and identies

increased emotional speechlessness in individuals with a total sum score

of > 29 [1].

Methods: A total of N = 621 oncology patients were assessed for

speechlessness using the KFS; 75.5% of respondents provided complete

information.

Results: A total of n = 343 patients scored a total sum score > 29. Male

patients (n = 108) scored a signicantly lower total sum score (t(467)

= -2.592; p = .01; d = 17.9) and have a lower relative risk (RR = .84;

p = .028; 95% CI: .72 - .98) of suprathreshold speechlessness. Patients with

a diagnosis > 5 years (n = 141) scored signicantly lower (t(467) = 2.885;

p = .004; d = 17.87) than patients whose diagnosis was < 5 years (n =

328) and have a signicantly lower Releative Risk (RR = .85; p = .02; 95%

CI: .75 - .98) of suprathreshold speechlessness.

Discussion: Patients whose diagnosis and associated therapy (and bur-

den) occurred longer ago exhibit signicantly lower emotional speech-

lessness. It can be assumed that an oncological disease increases the

occurrence of emotional speechlessness.

Conclusions: Speechlessness in the context of oncologic disease should

be further explored.

Indication of source

1 Dietz et al. (2021). Kölner Fragebogen zur Sprachlosigkeit. Psychotherapeut.

https://doi.org/10.1007/s00278-021-00541-2

2 Dietz et al. (2022). Kölner Fragebogen zur Sprachlosigkeit: Entwicklung und

Validierung. Köln.

Disclosure Statement: e authors declare no conict of interest. e project was

nancially supported by the Barbara and Wilfried Mohr Foundation.

869

Treatment of immune thrombocytopenia (ITP) with

eltrombopag – results of the 5th interim analysis of the

German non-interventional trial RISA

Oliver Meyer1; Rudolf Schlag2; Thomas Stauch3; Bastian Fleischmann4;

Marcel Reiser5; Dietrich Kämpfe6; Timo Behlendorf7; Manfred Welslau8;

Eyck von der Heyde9; Steen Dörfel10; Claudia Willy11; Martina Stauch12

1DRK-Blutspendedienst NSTOB, Springe, Deutschland

2Hämatologisch-Onkologische Schwerpunktpraxis, Würzburg, Deutschland

3MEDIAN Reha-Zentrum, Bad Berka, Deutschland

4Cancer Center Dachau, Onkologisches Zentrum, Donauwörth, Deutschland

5PIOH Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland

6Praxis für Hämatologie und Onkologie, Lüdenscheid, Deutschland

7Gemeinschaftspraxis und Tagesklinik, Innere Medizin – Hämatologie –

Onkologie – Gastroenterologie – Palliativmedizin, Halle (Saale), Deutschland

8Onkologie Aschaenburg, Hämato-Onkologische Schwerpunktpraxis am

Klinikum Aschaenburg, Aschaenburg, Deutschland

9Onkologische Schwerpunktpraxis, Hannover, Deutschland

10Onkozentrum Dresden/Freiberg, Dresden, Deutschland

11Novartis Pharma GmbH, Nürnberg, Deutschland

12Ambulantes Zentrum für Hämatologie, Onkologie und Gerinnung, Kronach,

Deutschland

Background: Eltrombopag (EPAG) is a thrombopoietin-receptor agonist

approved for the second line treatment of ≥1 year old patients with pri-

mary immune thrombocytopenia (ITP) ≥6 months aer initial diagnosis.

Methods: RISA is a single-cohort, non-interventional, multicenter obser-

vational study, evaluating the treatment of ITP patients with EPAG. In

addition to hematological parameters, evaluation of fatigue, based on the

FACIT-F score, was part of the monthly examinations.

Result: Data cuto for this 5th interim analysis was 11.02.2022. 302

enrolled patients had at least one post-baseline visit. Median platelet

count increased from baseline 34.0x109/L (N=292) to 91.5x109/L (N=262)

and 108.0x109/L (N=146) within one month and 12 months, respectively.

Aer one month from baseline until the end of the observation period,

platelet counts remained stable above 90x109/L. e number of bleeding

events per patient-year decreased, from 1.35 at baseline to 0.59 aer one

year and to 0.16 aer two years. is corresponds to a reduction of yearly

bleeding events by 56% and 88% within the rst and second year, respec-

tively. At baseline, FACIT-F score indicated severe fatigue (N=233; mean

36.2; range 7–52). Aer 12 months, mean FACIT-F score was 38.5 (N=93;

range 1–52). In general, EPAG has been well tolerated. No new safety

signals were identied.

Discussion: Descriptive analyses suggested that EPAG therapy increased

the platelet count and reduced bleeding events, without any evidence of

new safety concerns. Fatigue is a signicant issue in patients with ITP, but

the eect of EPAG treatment on fatigue seems less pronounced than the

eect on platelet count and bleeding events.

Conclusion: EPAG is an eective and safe therapy for ITP. Within the

rst month of treatment, the platelet count increases and then remains

stable over a long period of time. Within two treatment years, the inci-

dence of bleeding events decreases by up to 88%. EPAG is less eective in

treating fatigue than in increasing platelet counts and reducing the risk

of bleeding.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts190

914

Use of patient versions of oncological clinical practice

guidelines in Germany - rst results of a qualitative study

Sarah Wahlen1; Jessica Breuing1; Monika Becker1; Stefanie Bühn1;

Nadja Könsgen1; Julia Hauprich1; Nora Meyer1; Susanne Bloedt2;

Ernst-Guenther Carl3; Markus Follmann4; Stefanie Frenz5; Thomas Langer4;

Monika Nothacker2; Corinna Schaefer6; Dawid Pieper7

1Institut für Forschung in der Operativen Medizin (IFOM), Universität Witten/

Herdecke, Köln, Deutschland

2Institut für Medizinisches Wissensmanagement, Arbeitsgemeinschaft der

Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) c/o Philipps-

Universität, Marburg, Deutschland

3Bundesverband Prostata Selbsthilfe e.V., Bonn, Deutschland

4Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft e.V, Berlin,

Deutschland

5Frauenhilfe Krebs Bundesverband e.V, Bonn, Deutschland

6Ärztliches Zentrum für Qualität in der Medizin (ÄZQ), Berlin, Deutschland

7Institut für Versorgungs- und Gesundheitssystemforschung und Zentrum

für Versorgungsforschung Brandenburg (ZVF-BB), Medizinische Hochschule

Brandenburg, Rüdersdorf bei Berlin, Deutschland

Background: Patients with cancer evolve information needs, which are

oen not fully addressed. Patient versions of clinical practice guidelines

(PVoGs) oer evidence based information in plain language. e purpose

of this study is to examine the use and dissemination of PVoGs from the

patient’s perspective in Germany.

Methods: Between September and November 2021, n=30 semi-struc-

tured telephone interviews with oncological patients were conducted.

Selected PVoGs were given to participants beforehand. e interviews

were analyzed with qualitative content analysis (Mayring) supported by

MAXQDA soware.

Result: e participants were predominantly female (60%) and 50% of the

participants had no awareness of the existence of PVoGs before participa-

tion. Aer reading the PVoGs all of the participants would recommend

them. e majority of participants consider the comprehensibility of

PVoGs to be good. According to the experiences of the participants, phy-

sicians hold an important role in information provision, but rarely refer

to or recommend PVoGs. ere are dierent opinions on PVoGs format

between patients. Some would prefer an app, while others would stick to

print or pdf. Age is stated by participants as a potential factor in the pref-

erence of format. An interactive use of the PVoGs is oen requested espe-

cially in the context of physician-patient communication, e.g. physicians

highlighting patient relevant details in text.

Discussion: Since physicians are essential to patients in information pro-

vision, the dissemination of PVoGs could be increased through active

handover within clinical appointments. Additionally, PVoGs could

improve patient-physician communication.

Conclusion: PVoGs are evidence-based patient information, which

are partially known by patients and poorly established in patient care.

Professionals could help to increase the dissemination and implementa-

tion of PVoGs in daily practice. Further research should investigate the

appropriateness of dierent formats of PVoGs.

Disclosure Statement: Some authors declare conict of interest.

1014

COVID-19 in cancer patients – higher inammatory response

in patients with active cancer

Maria Madeleine Rüthrich1,2,3; Yascha Khodamoradi4; Julia Lanznaster5;

Melanie Stecher6,7; Lukas Tometten8; Florian Voit9; Carolin E.M. Jakob6,7;

Stefan Borgmann10; Jörg Janne Vehreschild6,7,11; Bjoern-Erik Jensen12;

Frank Hanses13; Clemens Giessen-Jung14; Kai Wille15;

Marie von Lilienfeld-Toal3,16; Gernot Beutel17

1University Hospital Jena, Centre of Emergency Medicine, Jena, Deutschland

2University Hospital Jena, Institute of Medical Statistics, Computer and Data

Sciences, Jena, Deutschland

3Leibniz-Institut für Natursto-Forschung und Infektionsbiologie - Hans-Knöll-

Institut, Leibniz Institute for Natural Product Research and Infection Biology,

Jena, Deutschland

4University Hospital Frankfurt, Goethe University, Department of Internal

Medicine, Infectious Diseases, Frankfurt, Deutschland

5Passau Hospital, Department of Internal Medicine II, Passau, Deutschland

6University of Cologne, Faculty of Medicine and University Hospital Cologne,

Department I of Internal Medicine, Center for Integrated Oncology Aachen

Bonn Cologne Duesseldorf , Deutschland

7German Centre for Infection Research (DZIF), partner site Bonn-Cologne,

Cologne, Deutschland

8University Hospital of Cologne, Department I for Internal Medicine, Cologne,

Deutschland

9University Hospital Rechts der Isar, Technical University of Munich, School of

Medicine, Munich, Deutschland

10Ingolstadt Hospital, Department of Infectious Diseases and Infection Control,

Ingolstadt, Deutschland

11Goethe University, Department II of Internal Medicine, Hematology/Oncology,

Frankfurt am Main, Deutschland

12Heinrich Heine University, Department of Gastroenterology, Hepatology and

Infectious Diseases, Düsseldorf, Deutschland

13University Hospital Regensburg, Emergency Department, Regensburg,

Deutschland

14Ludwig Maximilian University, Department of Internal Medicine III, Munich,

Deutschland

15University of Bochum, University Clinic for Hematology, Oncology,

Hemostaseology and Palliative Care, Minden, Deutschland

16University Hospital Jena, Department of Internal Medicine II, Hematology and

Medical Oncology, Jena, Deutschland

17Hannover Medical School, , Department for Haematology, Haemostasis,

Oncology and Stem Cell Transplantation, Hannover, Deutschland

Background: Active cancer has been identied as an independent risk

factor for severity and mortality in COVID-19. However, direct compar-

isons of SARS-CoV-2 infected patients (pts) with active and non-active

cancers remain scarce.

Methods: We retrospectively analyzed a cohort of pts with cancer with

conrmed SARS-CoV-2 infection, enrolled 03/16/2020 – 07/31/2021.

Data on demographics, cancer and laboratory ndings were collected.

Descriptive and subsequent regression analysis was performed. Endpoints

were progression to severe COVID-19 and infection-associated mortality.

Result: In total, 987 pts with cancer (510 active vs 477 non-active) were

included in our analysis. Majority was male and > 55 years, with a higher

number of elderly pts with non-active cancer. CCI was 4.75 vs 3.85 in pts

with active and non-active cancer (p<0.001). Localized solid tumors were

reported in 38 vs 79% (p<0.001), metastasized in 37.5 vs 5.5% (p<0.001)

and hematological diseases in 37.5 vs 19.5% (p<0.001) pts with active and

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 191

non-active cancer, respectively. At virus detection, majority of pts showed

mild to moderate symptoms, while deterioration to severe COVID-19 was

slightly more common in pts with active cancer (19% vs 16%; p=0.284).

COVID-19 related mortality was signicantly higher in pts with active

cancer (24% vs 17.5%, p<0.001). In line, severe cytopenia and an increase

of inammatory markers were common ndings in pts with active cancer

at baseline, particularly in those who developed severe infection or died.

Multivariate analysis revealed that ferritin (14.24 [2.1–96], p=0.006) and

CRP (2.85 [1.02–8.02], p=0.046) were associated with severe COVID-19

and infection-related mortality. In pts with non-active cancer, association

was seen for ferritin only (4.1 [1.51–11.17], p=0.006).

Conclusion: Comparing pts with active and non-active cancer, mortality

rate was signicantly higher in pts with active cancer. Also inammatory

markers were signicantly increased assuming higher levels of inamma-

tion may play a role in adverse outcome of COVID-19 in pts with active

cancer.

Disclosure Statement: e authors declare no conict of interest.

1041

Seasonal community acquired respiratory viruses (CARV)

are associated with a high burden of disease in patients with

malignancies – preliminary data of the OncoReVir registry

Maria Madeleine Rüthrich1,2,3; Timo Schmitt4; Annika Y. Claßen5,6;

Michael von Bergwelt-Baildon7; Yascha Khodamoradi8;

Anna Dorottya Doleschall9,10; Larissa Henze11; Jena Panse9,10;

Gabriel Sauer8; Karsten Spiekermann7; Enrico Schalk12;

Maria Vehreschild8; Janne Jörg Vehreschild5,6,10,13; Daniel Teschner14;

Marie von Lilienfeld-Toal3,15; Nicola Giesen16

1University Hospital Jena , Centre of Emergency Medicine, , Jena, Deutschland

2University Hospital Jena, Institute of Medical Statistics, Computer and Data

Sciences, Jena, Deutschland

3Hans-Knöll Institute, Leibniz Institute for Natural Product Research and

Infection Biology, Jena, Deutschland

4University Medical Center of the Johannes Gutenberg-University, Department

of Hematology, Medical Oncology and Pneumology, Mainz, Deutschland

5University of Cologne, Faculty of Medicine and University Hospital Cologne,

Department I for Internal Medicine, Cologne, Deutschland

6German Centre for Infection Research (DZIF), partner site Bonn-Cologne,

Cologne, Deutschland

7University Hospital, Ludwig Maximilian University (LMU) Munich, Department

of Internal Medicine III, Munich, Deutschland

8Universitay Hospital Frankfurt, Goethe University, Department of Internal

Medicine, Infectious Diseases, Frankfurt am Main, Deutschland

9University Hospital RWTH Aachen, Department of Hematology, Oncology,

Hemostaseology and Stem Cell Transplantation, Aachen, Deutschland

10Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf

(ABCD), Deutschland

11Rostock University Medical Center, Department of Medicine, Clinic III –

Hematology, Oncology, Palliative Medicine , Rostock, Deutschland

12Otto-von-Guericke University Magdeburg, Department of Haematology and

Oncology, Medical Centre, Magdeburg, Deutschland

13University Hospital Frankfurt, Goethe University, Department II of Internal

Medicine, Hematology/Oncology, Frankfurt, Deutschland

14Department of Internal Medicine II, University Hospital Würzburg, Würzburg,

Deutschland

15University Hospital Jena, Department of Internal Medicine II, Hematology and

Medical Oncology, Jena, Deutschland

16University Hospital Heidelberg, Department of Haematology and Oncology,

Internal Medicine V, Heidelberg, Deutschland

Background: Community acquired respiratory viruses (CARVs) may

cause severe respiratory infections in patients (pts) with cancer.To col-

lect epidemiological and clinical data of CARV-infections the multicentric

registry OncoReVir was established. Here, we present a preliminary anal-

ysis of pts with cancer infected with CARVs.

Methods: A total of 1,142 pts with cancer and CARV-infection were

enrolled betweenNov2018andJan2022. Most cases were documented for

season 17/18 and 18/19. Data on demographics, comorbidities, cancer,

CARVs and infection course were collected. Pre-dened endpoints were

pneumonia, admission to ICU and mortality. e relationship between

cancer-specic factors and outcome was evaluated by bivariate logistic

regression.

Result: e median age was 60 (IQR 50–67) years, 42% of pts were female.

Solid tumors were present in < 10%, leukemia, lymphoma and multiple

myeloma in 36.5%, 27% and 23%, respectively. 50% had active cancer, 40%

had received chemotherapy within the last 3 months. Targeted therapy

was reported in 11.5%, high-dose steroids in 16% of pts, 56% were SCT-

recipients. Commonly detected CARVs were inuenza (39.5%), parainu-

enza (18%), respiratory syncytial virus (15%), rhinovirus (14.5%), human

metapneumovirus (hMPV, 5.5%), endemic coronavirus (5.5%) and SARS-

CoV-2 (2%). Among all CARVs, frequent symptoms were cough, fever,

dyspnea and rhinitis. Rates of pneumonia were highest in hMPV (33%)

and SARS-CoV-2 (32%), lowest in endemic coronavirus (16%, p=0.334).

8.5% required intensive care, most of them due to COVID-19 (p=0.084).

Infection-associated mortality but not rate of pneumonia showed signif-

icant dierences comparing CARVs. In regression analysis, active cancer

was associated with all endpoints: infection-related mortality (4.02 [1.63–

9.88], p=0.002), ICU admission (1.75 [1.07–2.88], p= 0.027) and pneumo-

nia (1.47 [1.1–1.96], 0.009).

Conclusion: In our cohort, all CARVs could potentially lead to severe

disease. Active cancer was an independent risk factor for adverse outcome

in pts with cancer and CARV-infection.

Disclosure Statement: e authors declare no conict of interest.

1061

Pathogenic germline variants in BRCA and pregnancy

rates – data from a German Center of Hereditary Breast

and Ovarian Cancer

Susan Friedrich1,2; Dorothee Speiser1,2

1Charité - Universitätsmedizin Berlin, Klinik für Gynäkologie und

Geburtsmedizin, Berlin, Deutschland

2Charité - Universitätsmedizin Berlin, Zentrum Familiärer Brust- und

Eierstockkrebs, Berlin, Deutschland

Purpose: Women with pathogenic germline variants in BRCA1/2

presumably have a lower ovarian reserve.1

An overview of reproduction-associated problems of BRCA mutation

carriers (MC) compared to women without a pathogenic genetic variant

(PV) helps to counsel women with PV in fullling their desire to have

children in the future.

Methods: e study cohort included women with pathogenic germline

variants in BRCA detected at the Charité Center of Hereditary Breast and

Ovarian Cancer. Counselees and patients who have been tested nega-

tive before served as control group. Pregnancy rates and outcomes were

recorded through a questionnaire.

Results: 229 women were included in the study. e study population

consisted of 166 (72%) BRCA MC (between 18 and 80 years old). e

control population consisted of 63 (28%) women without a PV. e pro-

portion of nulligravida was 30.5% in the BRCA-subset and 22.6% in the

control group (p=0.55). Among BRCA MC, women reported 1.13, in the

control group 1.26 (p=0.40) live births. 6% of the BRCA-carriers needed

reproductive assistance in contrast to 1.6% of the control group (p=0.17).

e average age for 1st birth in BRCA MC is 28.5 years and without PV it

is 27.3 years (p=0.18).

Conclusions: e results support studies that have already indicated

lower ovarian reserve in BRCA MC, due to lower AMH-levels.2 Although

no signicant dierence in the number of nulligravidae or the number

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts192

of reproductive assistance could be established in our study, there was a

trend that women with PVs in BRCA seemed to have more diculties get-

ting pregnant. Larger cohort studies throughout Germany could conrm

this eect in the future.

(1) Oktay, Kutluk et al. “Association of BRCA1 mutations with occult pri-

mary ovarian insuciency: a possible explanation for the link between

infertility and breast/ovarian cancer risks.”Journal of clinical oncology

vol. 28,2 (2010): 240-4.

(2) Gasparri, Maria Luisa et al. “Ovarian reserve of women with and

without BRCA pathogenic variants: A systematic review and

meta-analysis.”Breast)vol. 60 (2021): 155-162.

Disclosure Statement: e authors declare no conict of interest.

1067

Qualitative methods for the evaluation of counseling sessions

in oncology

Jasmin Bossert1; Bianca Korus1; Helena Dürsch1; Ursula Boltenhagen2;

Mette Stie3,4; Nadja Klafke1

1Universitätsklinikum Heidelberg, Abteilung Allgemeinmedizin und

Versorgungsforschung, Heidelberg, Deutschland

2Universitätsklinikum Tübingen, Institut für Gesundheitswissenschaften und

Pegewissenschaften, Tübingen, Deutschland

3Lillebaelt Hospital, University Hospital of Southern Denmark, Department of

Oncology, Middelfart, Dänemark

4University of Southern Denmark, Department of Regional Health Research,

Faculty of Health Sciences, Odense, Dänemark

Background: Qualitative evaluation of oncology consultations is an

opportunity to gain insight into the communication between healthcare

providers and patients in order to give them the opportunity to actively

participate in their treatment. erefore, the aim of this scoping review is

to provide an overview of existing qualitative evaluation methods used in

the context of monoprofessional as well as interprofessional consultations.

Methods: We included all study types reporting on qualitative methods,

including mixed-methods studies, to analyse patient-provider consulta-

tions which were published from 1990 - 2020. We required databases to

identify relevant articles. Quality assessment was performed by the JBI

checklist for Qualitative Research.

Result: A total of 67 studies were included in this review (64 monoprofes-

sional, 3 interprofessional consultations). e most common counselling

context was treatment management, and oncological patients were most

frequently counselled. A total of 86 dierent qualitative analysis meth-

ods were identied, while content analysis was the most commonly used

method. One advantage of this method is the step-by-step procedure

using previously explained techniques. A disadvantage of the method

is that non-verbal aspects are not considered. Other possibilities for the

qualitative analysis of consultations are represented by grounded theory

and conversation analysis.

Discussion: Patient-centred communication is important in cases of seri-

ous illness. Integrating the analysis of patient-provider consultations is

one way to strengthen the latter. Qualitative methods which can be used

for analysis all oer advantages and disadvantages. Researchers should be

aware of these and weigh which method is best for their purposes.

Conclusion: is scoping review highlights dierent techniques for eval-

uating consultations and is intended to be a guide for other researchers

studying patient-provider communication to strengthen patient-centred

communication.

Disclosure Statement: e authors declare no conict of interest.

1068

Impact of the COVID-19 pandemic on GP care: Results

of a national survey in Germany

Tugba Aksakal1; Yüce Yılmaz-Aslan1,2,3; Patrick Brzoska1

1Universität Witten/Herdecke, Fakultät für Gesundheit, Department für

Humanmedizin, Lehrstuhl für Versorgungsforschung, Witten, Deutschland

2Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG3

Epidemiologie und International Public Health, Bielefeld, Deutschland

3Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG6

Versorgungsforschung und Pegewissenschaft, Bielefeld, Deutschland

Background: GP practices in Germany are facing many challenges due

to the COVID 19 pandemic. In addition to the general care of patients,

infection control measures and obligations in existing testing and vacci-

nation strategies led to an increased workload. e aim of this cross-sec-

tional study was to assess the ongoing and new workload related to the

pandemic, such as additional burden caused by booster vaccinations.

Furthermore, restrictions, e.g., on GP cancer screening and treatment,

were examined.

Methods: In December 2021 and January 2022, general practitioners

in Germany were invited to participate in a nationwide online survey

(n=3,050). e questionnaire was used to assess the impact of the pan-

demic on GP care. Responses were received from a total of 314 GP prac-

tices. Results were analysed descriptively.

Result: Challenges, restrictions and burdens resulting from the pan-

demic were still prevalent in GP practices at the time of the survey. e

additional need for the education of patients unwilling to get vaccinated

because of misinformation, as well as the diculties in the vaccination

campaign, e.g. delivery problems, were considered problematic. Including

vaccinations into work processes or impatience and lack of understanding

on the part of the patients were seen as particularly burdensome. GPs also

perceived a negative impact on cancer prevention and treatment.

Discussion: Adequate patient education can contribute to reducing mis-

information and thereby easing the workload in GP practices. Practical

guidelines can help to ensure adequate health care even in times of crisis

and also to protect particularly vulnerable patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 193

Paediatric Cancer

Best-of-Abstract-Vortrag

737

Medulloblastoma with extensive nodularity mimics cerebellar

development and dierentiates along the granular precursor

lineage

David Ghasemi1; Konstantin Okonechnikov2; Stephan Tirier3;

Anne Rademacher3; Jan-Philipp Mallm4; Kati Ernst5; Karsten Rippe4;

Stefan Pster1; Andrey Korshunov6; Kristian Pajtler1

1Hopp-Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,

Division of Pediatric Neuro-oncology, German Cancer Consortium (DKTK),

German Cancer Research Center (DKFZ), Heidelberg, Germany, Department

of Pediatric Oncology, Hematology, and Immunology, University Hospital

Heidelberg, Heidelberg, Germany, Heidelberg, Deutschland

2Hopp-Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,

Division of Pediatric Neuro-oncology, German Cancer Consortium (DKTK),

German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg,

Deutschland

3Division of Chromatin Networks, German Cancer Research Center (DKFZ) and

Bioquant, Heidelberg, Germany, Heidelberg, Deutschland

4Division of Chromatin Networks, German Cancer Research Center (DKFZ) and

Bioquant, Heidelberg, Germany, Single-cell Open Lab, German Cancer Research

Center (DKFZ), Heidelberg, Germany, Heidelberg, Deutschland

5Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ),

Heidelberg, Germany, Heidelberg, Deutschland

6Hopp-Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,

Department of Neuropathology, Institute of Pathology, Heidelberg University

Hospital, Heidelberg, Germany, Heidelberg, Deutschland

Background: Medulloblastoma with extensive nodularity (MB/ MBEN)

represents a rare entity of cerebellar tumours of infancy comprising two

histologically distinct components that dier in cell dierentiation and

mitotic activity. While some children suering from MBEN experience

disease recurrence, MBEN can also dierentiate into benign tumours.

e underlying mechanisms of this variable biological behaviour remain

poorly understood but may oer insight into how cerebellar tumours of

infancy develop.

Methods: Fresh frozen tissue of nine MBEN-patients was subjected to a

multi-omics approach including bulk sequencing, microdissection, sin-

gle nucleus RNA-sequencing using the 10X Genomics- and SMART Seq.

V2-protocols and spatial transcriptomics via the RNAscope-platform.

Result: All cases were classied as Sonic Hedgehog (SHH)-MB, and har-

boured somatic mutations within the SHH-pathway. Aer quality control,

~30.000 cells were subjected to downstream analysis. Several non-ma-

lignant cell types, such as glial cells, were identied. In accordance with

previous studies, we found only sparse immune inltration. Based on

unsupervised clustering, we identied clusters of MBEN-cells that dif-

fered strongly in dierentiation state and represented a continuum from

embryonal-like cells with SHH-upregulation over intermediate cell states,

to neuronal-like, postmitotic cells. ese tumour cells reected stages of

normally developing cerebellar granular precursors. Using spatial tran-

scriptomics, we were able to correlate dierent clusters of MBEN cells

with MBEN’s two histologic compartments.

Discussion: While our results suggest that MBEN mimics physiological

embryonal development, the exact mechanisms behind this biological

behavior remain to be unraveled.

Conclusion: MBEN tumors are formed by a continuum of heterogenic

malignant cells that dierentiate along the granular precursor lineage.

is dierentiation process is reected in the bicompartmental structure

of MBEN.

Disclosure Statement: e authors declare no conict of interest.

Poster

Feasibility and acceptance of an exercise program

for pediatric patients with advanced cancer - a pilot project

Ronja Beller; Gabriele Gauß; Dirk Reinhardt; Miriam Götte

Zentrum für Kinder- und Jugendmedizin, Kinderheilkunde III, Hämatologie/

Onkologie, West Deutsches Tumor Zentrum, Universitätsklinikum Essen, Essen,

Deutschland

Background: Growing evidence suggests benets of exercise programs in

pediatric oncology and, patients should have access to exercise programs

during all treatment phases including palliative care. is pilot analyzes

the feasibility of exercise programs oered during hospital and home-

based palliative care.

Methods: e exercise program consisted of individual, supervised and

resource-oriented interventions home based or inhospital at least once a

week in palliative care. It comprised training of i.e. strength, endurance,

coordination, and body awareness according to patients’ wishes and daily

condition. ree children (girl, 13yrs – sarcoma; boy, 7yrs – leukemia;

boy 12yrs – sarcoma) participated. Data collection of psychological and

physical endpoints was intended to be every 4-6 weeks.

Results: Adherence to planned exercise sessions was 73±9% in a par-

ticipation range of 3-18 weeks with 54% of interventions at home, 36%

inpatient and 11% outpatient. Patients accepted the oer until close to

their death (last intervention was 10±3 d before death). Mean duration of

interventions was 66±10 min. Longitudinal data could only be assessed

from one participant. Results indicate an increase of psychosocial health

although physical health score was low and still decreased. Isometric

handgrip strength decreased, whereas leg strength increased over time.

No adverse events have occurred in relation to exercise.

Discussion: Results indicate that exercise was safe, feasible, and well tol-

erated by patients. Although data collection was partially impossible, high

needs and acceptance of this program showed the importance of support-

ive exercise programs for young patients with advanced cancer.

Conclusion: e individually adapted exercise programs might serve as

a supportive tool to reduce overall burden. Children’s and parent’s needs

were respected. More research in this treatment phase is needed.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts194

201

Development of patient-derived xenograft (PDX) models from

high-risk childhood cancers for preclinical evaluation of novel

therapeutics

Dennis Gürgen1; Johannes H. Schulte2; Anton G. Henssen2,3,4; Angelika

Eggert2; Wolfgang Walther1,3,4; Jan Koster5; Louis F. Stancato6; Stefan

Pster7; Jens Homann1

1Experimental Pharmacology and Oncology Berlin Buch GmbH, Berlin,

Deutschland

2Department of Pediatrics, Charité University Clinic Berlin, Division of Oncology

and Hematology, Berlin, Deutschland

3Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Deutschland

4Experimental and Clinical Research Center (ECRC), Charité University Clinic

Berlin, Berlin, Deutschland

5Academic Medical Center (AMC), Department Oncogenetics, Amsterdam,

Niederlande

6Eli Lilly and Company, PEDS Hub, Indianapolis, USA

7German Cancer Research Center (DKFZ), Division of pediatric Neurooncology,

Heidelberg, Deutschland

Background: Neuroblastoma (NB) and sarcomas represent aggressive

pediatric malignancies with highly variable clinical outcomes of imme-

diate fatal progression or spontaneous regression. Pronounced rates of

relapse, fast evolving resistance against standard-of-care (SOC) therapies

and a high degree of mutational mobility and heterogeneity indicate the

need for more precise and molecular targeted therapies.

Methods: Within the framework of the European IMI2 ITCC-P4 project

(Grant Agreement No 116064), we established a cohort of 10 NB and 35

pediatric PDX models of Ewing, osteo- and rhabdomyosarcoma (RMS)

closely resembling the human tumor architecture and molecular prole.

Aer stable growth of PDX models for 3-4 initial subcutaneous trans-

planted in vivo passages in immunodecient NOG mice, all models were

screened for sensitivity to selected SOC drugs and representative targeted

therapies.

Result: Pathology of all PDX models was veried using HE and IHC

staining of FFPE tumor sections. PDX doubling times dramatically varied

between 4 days in aggressive, 8 days in intermediate and up to 21 days in

slowly growing tumors. Strong in vivo ecacy was observed with SOC

drugs topotecan, cisplatin+cyclophosphamide in NB and trofosphamide,

actinomycin D+vincristine in RMS PDX models, though concomitant

with more pronounced side eects, especially in the combination treat-

ment. Interestingly, novel targeted therapies achieved similar anti-tumor

activity accompanied with good in vivo tolerability. Extensive analysis of

primary biopsies and PDX tumors utilizing whole-exome sequencing will

complete molecular characterization enabling translation of our pre-clin-

ical results.

Conclusion: Our pediatric PDX cohort is a powerful tool for further e-

cacy evaluation of targeted therapies in comparison to SOC compounds.

In vivo ecacy data together with PDX specic molecular proles will

support accelerated development of promising treatment regimens for

high risk pediatric cancers opening new therapeutic options and valuable

benets for pediatric patients.

Disclosure Statement: e authors declare no conict of interest.

625

A physical activity program on cardiorespiratory tness in

children and adolescents following acute cancer treatment

(POWER): study protocol for a randomized controlled trial

Miriam Götte1; Sandra Goertz2; Corina S. Rueegg3; Lisa Maas2;

TimNiehues2; Wolfgang Lawrenz4; Dirk Reinhardt1; Nina Brauer2

1Universitätsklinikum Essen, Klinik für Kinderheilkunde 3, Hämatologie/

Onkologie, Essen, Deutschland

2Helios Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Abteilung für

päd. Hämatologie und Onkologie, Krefeld, Deutschland

3Oslo University Hospital, Oslo Centre for Biostatistics and Epidemiology (OCBE),

Oslo, Norwegen

4Helios Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin,

Kinderkardiologie, Krefeld, Deutschland

Background: Treatment of pediatric cancer is associated with reduced

physical activity and performance as well as an increased risk to develop

chronic health conditions. It has been shown that VO2peak is reduced

both during and aer childhood cancer treatment. Regular exercise may

play a major role to preserve cardiorespiratory tness and to mitigate

sequelae. Primary aim of the POWER-RCT is to evaluate the eective-

ness of a partially supervised 12-week physical activity program on car-

diorespiratory tness (VO2peak) in pediatric cancer patients who have

recently completed treatment. Secondary outcomes are muscular strength,

functional mobility, coordination, cognitive function, changes in blood

and echocardiography parameters, physical activity levels, health related

quality of life, and fatigue.

Methods: A total of n=56 pediatric cancer patients aged ≥7 and <23 years,

who are 6 weeks post cancer therapy will be recruited. Following baseline

assessments, patients are randomized 1:1 into an intervention (IG) and a

control group (CG). e IG receives a multimodal partially supervised

12-week exercise program consisting of individual and group training ses-

sions. Participants of both groups receive a brochure with recommended

exercises and daily physical activities as well as a tness tracker to measure

the minutes of moderate to vigorous physical activities. Cardiorespiratory

performance, other physical, psychological, cognitive, and immunological

parameters are investigated in both groups.

Results: e POWER trial will provide insight into the eectiveness of an

early-administered physical activity program for pediatric cancer patients.

It might be a simple way to prevent future long-term treatment eects and

improve the general health state of these children.

Discussion: If eective, the intervention content will be translationally

implemented in the care setting of children and adolescents with cancer.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 195

823

Barriers to childhood cancer care in Sub-Saharan Africa –

a multinational, population-based cohort study

Ole Stöter1; Nikolaus Mezger1; Tamara König1; Ima-Obong Ekanem2,3;

Girum Tessema Zingeta4; Mathewos Assefa3,5,6; Franck Gnahatin3,7;

Henry Wabinga3,8; Mamadou Kéïta9; Eva Johanna Kantelhardt1,10

1Institute of Medical Epidemiology, Biometrics and Informatics, Martin‐Luther‐

University Halle‐Wittenberg, Halle (Saale), Deutschland

2Department of Pathology, University of Calabar, Calabar, Nigeria

3The African Cancer Registry Network, INCTR African Registry Programme,

Oxford, Vereinigtes Königreich

4Oncology Department, Tikur Anbessa Specialized Hospital, School of Medicine,

Addis Ababa University, Addis Ababa, Äthiopien

5Radiotherapy Center, Tikur Anbessa Specialized Hospital, Addis Ababa,

Äthiopien

6Addis Ababa Cancer Registry, Addis Ababa, Äthiopien

7Registre des cancers d’Abidjan, Abidjan, Côte d’lvoire

8Kampala Cancer Registry, Makerere University School of Medicine, Kampala,

Uganda

9Service du Laboratoire d’Anatomie et Cytologie Pathologique, CHU du point G,

Bamako, Mali

10Department of Gynaecology, Martin‐Luther‐University Halle‐Wittenberg, Halle

(Saale), Deutschland

Purpose: e WHO Global Initiative for Childhood Cancer aims to reach

60% survival rate by 2030 worldwide. For improved outcomes in child-

hood cancer (CC), it is decisive to start treatment swily, yet uptake of CC

care in Sub-Saharan Africa (SSA) is oen low and delayed. We conducted

a study to provide a comprehensive overview of barriers to CC care in

real-world patients in the region.

Methods: Our questionnaire study covers nine population‐based cancer

registries in nine countries across all Sub-Saharan regions (East, South,

Central, and West). Per registry, random samples of 20 to 50 patients diag-

nosed with any childhood cancer (age 0-19) between 2017 and 2019 were

selected. Patients, or their main caretakers were interviewed and data on

modality-specic barriers to chemotherapy, radiotherapy, and surgery

were collected.

Results: A total of 225 CC cases were included. Median age was 5 years

and the majority of patients was male. Over 80% of all CC patients

reported receipt of any cancer-directed therapy (surgery, radiotherapy or

chemotherapy), the majority receiving chemotherapy. Concerning barri-

ers to care, the perceived bad health status and the fear of side eects and/

or consequences of the treatment modality were named most frequently

as problematic (surgery 77.6% and 77.5%; radiotherapy 80.6% and 78.0%;

chemotherapy 73.9% and 80.6%). e results diered by region. For

example, a (high) cost of treatment was frequently considered problem-

atic in Eastern, Western and Central Africa but not in Southern Africa.

Discussion: In SSA, the availability of diagnostic services and treatment

facilities is widely considered most crucial to improve cancer care and

hence survival. Our study indicates that the perceptions and beliefs of

families of CC patients concerning the disease and its treatment prove to

be as important.

Conclusion: Patient education initiatives and health professional train-

ings should increasingly address concerns of caretakers and inform about

circumstances of cancer treatment to improve uptake of care and thus

prognosis of CC patients.

Disclosure Statement: e authors declare no conict of interest.

829

Analysis of cell-free dna in the plasma of patients with

non-resectable, progressive or relapsed pediatric

malignancies

Kendra K. Maass1,2; Pitithat Puranachot3,4; Paulina S. Schad1;

Agnes M.E. Finster1; Barbara Jones2,5,6; Tatjana Wedig1,2;

Nathalie Schwarz1; Petra Fiesel5,7,8; Gnanaprakash Balasubramanian1,3;

Jochen Meyer7,9; Felix Sahm5,7,9; Stefanie Zimmermann10;

David T.W. Jones5,6,8; Benedikt Brors3,8; Stefan M. Pster1,2;

Kristian W. Pajtler1,2

1Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,

Division of Pediatric Neurooncology, German Cancer Consortium (DKTK),

German Cancer Research Center (DKFZ), Heidelberg, Germany

2Department of Pediatric Oncology, Hematology, Immunology and

Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

3Division of Applied Bioinformatics, German Cancer Research Center (DKFZ),

Heidelberg, Germany

4Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of

Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand

5Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany

6Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ),

Heidelberg, Germany

7Department of Neuropathology, Institute of Pathology, Heidelberg University

Hospital, Heidelberg, Germany

8German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Germany

9Clinical Cooperation Unit Neuropathology, German Consortium for

Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Germany

10Department of Pediatric Hematology and Oncology, University Hospital

Frankfurt, Frankfurt, Germany

Cell-free DNA (cfDNA) released by tumor cells provides the opportunity

to improve diagnosis and treatment using minimally invasive approaches

to molecularly survey clinically informative biomarkers and ‘action-

able’ targets. e ‘Individualized erapy for Relapsed Malignancies in

Childhood’ (INFORM) registry aims to identify actionable therapeutic

targets on a personalized basis. Relapsed or refractory high-risk tumors as

well as selected rare entities, for which no further standard of care therapy

is available, are characterized by state-of-the-art next-generation sequenc-

ing (NGS) technologies. Our study aims at integrating liquid biopsies into

the diagnostic INFORM pipeline and pave the way for clinical translation

of these technologies.

CfDNA for various downstream analyses is derived from plasma sam-

ples and isolated according to optimized protocols. Depending on the

yield of cfDNA, data availability for the primary tumor, and tumor entity,

we have performed low-coverage whole-genome sequencing (lcWGS),

whole exome sequencing (WES) and targeted gene panel sequencing.

Results are being compared with data obtained from standard tumor

biopsies and normal control tissues following adjustment of established

bioinformatics pipelines to suit liquid biopsy-derived data.

Sensitivity and specicity of our approach is presented as a proof-of-

concept study to compare the performance of dierent NGS platforms and

their utility for analyzing cfDNA samples. We demonstrate robust tumor

detection by lcWGS (n=115), mutation tracking by targeted approaches

(n=74) and the advantages of the combinatorial use of various approaches

(n=64).

We have demonstrated the feasibility of liquid biopsy analyses in

advanced pediatric malignancies. We highlight the informative values of

the liquid biopsy methods applied in terms of tumor detection, assess-

ment of tumor heterogeneity, and identication of actionable targets. Our

study is expected to guide and accelerate the implementation of liquid

biopsies into prospective pediatric clinical trials.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts196

934

Care, care needs and wellbeing of individuals after cancer in

childhood or adolescence (VersKiK)

Ekaterina Aleshchenko1; Thorsten Langer2; Gabriele Calaminus3;

Katja Baust3; Enno Swart1; Claudia Spix4; Pietro Trocchi1; Mathias Voigt4;

Peter Ihle5; Jutta Küpper-Nybelen5; Christian Lüpkes6; Thorben Kloppe6;

Patrik Dröge7; Dirk Horenkamp-Sonntag8; Ursula Marschall9;

Melanie Klein10; Iris Meier8; Christian Apfelbacher1

1Otto-von-Guericke Universität, Medizinischen Fakultät, Institut für

Sozialmedizin und Gesundheitssystemforschung, Magdeburg, Deutschland

2Universität zu Lübeck, Klinik für Kinder- und Jugendmedizin, Abteilung für

Pädiatrische Onkologie und Hämatologie, Lübeck, Deutschland

3Rheinische Friedrich-Wilhelms-Universität Bonn, Zentrum für Kinderheilkunde,

Abteilung für Pädiatrische Onkologie und Hämatologie, Bonn, Deutschland

4Universitätsmedizin Mainz der Johannes Gutenberg-Universität Mainz, Institut

für Medizinische Biometrie, Epidemiologie und Informatik, Mainz, Deutschland

5Universität zu Köln, PMV forschungsgruppe, Köln, Deutschland

6OFFIS e.V., Oldenburg, Deutschland

7AOK-Bundesverband GbR, Berlin, Deutschland

8Techniker Krankenkasse, Hamburg, Deutschland

9BARMER, Berlin, Deutschland

10DAK Gesundheit Hamburg, Hamburg, Deutschland

Care, care needs and wellbeing of individuals aer cancer in childhood or

adolescence (VersKiK)

A relevant proportion of childhood cancer survivors suers from late

eects, caused by the cancer itself or its therapy. To enhance their well-

being, follow-up guidelines were developed both on national and inter-

national levels. However, implementation of current German follow-up

guidelines is challenging due to organisational reasons or limited consid-

eration of psychosocial needs of survivors.

e overarching aim of the study is to provide representative evidence

about late-eects and follow-up care as well as in-depth understanding of

the care needs of childhood cancer survivors. Further aims are to examine

the adherence to selected follow-up guidelines and to suggest improve-

ments to them.

e present mix-methods, non-interventional study will analyse

claims data from German statutory health insurance funds in combina-

tion with individually linked by independent trust-centre anonymous

data from the German Childhood Cancer Registry. Perceived needs of

survivors, their informal caregivers and health professionals involved will

be investigated through volunteer interviews and focus groups.

e suggested study design will provide comprehensive evidence about

late eects of childhood cancer based on the largest available set of unse-

lected health care data in Germany. e description of the physical and

psychological late eects for a selected group of cancer diagnoses will help

to identify potential limitations and, consequently, suggest improvements

to the existing follow-up guidelines. An additional insight into actual state

of follow-up care and needs of cancer survivors, their informal caregivers

and healthcare provider involved will lay the groundwork for an improve-

ment of existing follow-up guidelines and possibly lead to new additions.

Disclosure Statement: e authors declare no conict of interest.

1060

Study protocol: Eects of a low vs. moderate intense exercise

program on immune recovery during pediatric allo-HSCT

(ANIMAL)

Ronja Beller1; Gabriele Gauß1; Sabrina Bianca Bennstein2;

Carolina Chamorro-Vina3; Helmut Hanenberg1; Dirk Reinhardt1;

Miriam Götte1

1Zentrum für Kinder- und Jugendmedizin, Kinderheilkunde III, Westdeutsches

Tumor Zentrum, Universitätsklinikum Essen, Essen, Deutschland

2Institut für Transplantationsdiagnostik und Zelltherapeutika AG Uhrberg /

Natürliche Immunität, Universitätsklinik Düsseldorf, Düsseldorf

3Kids Cancer Care Foundation of Alberta, University of Calgary, Calgary, Kanada

Background: Pediatric cancer patients undergoing allogeneic

Hematopoietic Stem Cell Transplantation (allo-HSCT) are at high risk for

life-threatening infections and transplant-related complications. Clinical

outcome aer allo-HSCT is closely associated with immune reconstitu-

tion, i.e. natural killer (NK-) cell counts ~30 days aer transplantation. In

general, exercise increases NK-cells in healthy and patient populations. In

the allo-HSCT setting, exercise positively inuences tness and psycho-

logical parameters. is exploratory study will evaluate the eects of indi-

vidualized exercise programs on NK-cells (primary aim), other immune

reconstitution parameters, performance and psychological endpoints and

transplantation outcomes.

Methods: A total of n= 20 pediatric cancer patients ≥4 years old, treated

with allo-HSCT will be recruited. Following baseline assessments,

patients are randomized 1:1 into an experimental intervention group 1

(EG1) with moderate intense exercise training and an experimental inter-

vention group 2 (EG2) with low intensity exercise training. Both groups

participate in multimodal supervised exercise sessions for 3-5x/week for

20-40min each with dierent contents (animals represent dierent con-

tents) and therefore dierent training intensities. Aer discharge EG1

receives 1-2x/week training until day +100 aer allo-HSCT. Immune and

laboratory (e.g. NK- and innate lymphoid cell subsets, IL-6/-7/-15/-33)

as well as performance and psychological parameters and transplantation

outcomes will be assessed.

Results: e ANIMAL trial evaluates the inuence of dierent intense

exercise programs on innate immune system recovery for children and

adolescents undergoing allo-HSCT.

Discussion: is trial might show if exercise can be used as a support-

ive care option to inuence immune recovery and to reduce infections.

If benecial, exercise could serve as a low-cost strategy to reduce days of

hospitalization and overall burden of the treatment.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 197

Palliative Care

Best-of-Abstract-Vortrag

976

Eect of a communication skills training for physicians on

early communication about palliative care and end-of-life

issues in advanced cancer patients: A randomized-controlled

trial (PalliKOM)

Nele Harnischfeger1; Hilke M. Rath2; Hannah Brand3; Karl Haller4;

Nicola Rieder5,6; Bernd Alt-Epping5,6; Anne Letsch3; Peter Thuss-Patience4;

Aneta Schieferdecker1; Carsten Bokemeyer1; Corinna Bergelt2;

Karin Oechsle1

1Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

2. Medizinische Klinik und Poliklinik, Palliativmedizin, Hamburg, Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für

Medizinische Psychologie, Hamburg, Deutschland

3Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin

mit Schwerpunkt Hämatologie und Onkologie, Kiel, Deutschland

4Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische

Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie,

Berlin, Deutschland

5Universitätsmedizin Göttingen, Klinik für Palliativmedizin, Göttingen,

Deutschland

6Universitätsklinikum Heidelberg, Klinik für Palliativmedizin, Heidelberg,

Deutschland

Background: In advanced cancer care, a timely communication of issues

related to palliative care (PC) and the end of life (EoL) has several bene-

ts for patients and caregivers. Yet, physicians’ insecurities oen impede

timely addressing those issues. Hence, we developed a short interactive

communication skill training (CST: PalliKOM) aiming to strengthen phy-

sicians in early and adequate communication.

Methods: We evaluated the CST (2x 90 min.) within a randomized-con-

trolled trial (RCT) at ve sites in Germany. Internal or organ-specic

oncologists were randomized into intervention group (IG) and wait list

control group (CG). At two assessment points, they lead a videotaped

medical consultation with a simulated patient. e IG received the CST

in-between, the CG aerwards. e videotapes were rated by study sta

blinded to group membership. Primary outcome were the observed com-

munication skills addressing PC-related topics. Further self and externally

assessed data served as secondary outcomes. Univariate analyses of cova-

riance with baseline adjustment were carried out for analysis.

Result: 141 physicians (age: M(SD) = 32.7(6.3), 59.8% female) took

part in this RCT (nIG = 73, nCG = 68). e IG shows signicantly more

improvement in communication skills than the CG on 4 of 5 rating scales:

“emotions and empathy” (F(1,134) = 6.47, p = .012, partial η² = .045),

“opportunities and hope” (F(1,136) = 7.74, p = .006, partial η² = .054),

“addressing the end of life” (F(1,135) = 5.64, p = .019, partial η² = .040)

and “explaining the concept of palliative care” (F(1,138) = 15.63, p < .001,

partial η² = .102). Most secondary outcomes also improved signicantly.

Discussion: is PalliKOM-CST has proven eective in multidimen-

sional outcome parameters. Small to medium eect sizes might be due to

too high initial values in some areas.

Conclusion: A future implementation of the PalliKOM-CST will enhance

early communication of PC and EoL issues and thereby improve advanced

cancer care. Sponsored by the German Cancer Aid (DKH).

Disclosure Statement: e authors declare no conict of interest.

1062

Screening versus multidimensional assessment of symptoms

and psychosocial distress in cancer patients from the time of

incurability – a randomized study of the APM network

Stefanie Solar1; Florian Lordick2; Anja Mehnert3; Karin Oechsle4;

Birgitt van Oorschot5; Michael Thomas6; Johannes Wieditz7;

Thomas Asendorf7; Bernd Alt-Epping1,8

1Universitätsmedizin Göttingen, Klinik für Palliativmedizin, Göttingen,

Deutschland

2Universitäres Krebszentrum Universitätsklinikum Leipzig (UCCL), Leipzig,

Deutschland

3Universitätsklinikum Leipzig, Abteilung für Medizinische Psychologie und

Medizinische Soziologie, Leipzig, Deutschland

4Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie, Hamburg,

Deutschland

5Universitätsklinikum Würzburg (UKW), Würzburg, Deutschland

6Universitätsklinikum Heidelberg, Thoraxklinik Heidelberg, Heidelberg,

Deutschland

7Universitätsmedizin Göttingen, Institut für Medizinische Statistik, Göttingen,

Deutschland

8Universitätsklinikum Heidelberg, Klinik für Palliativmedizin, Heidelberg,

Deutschland

Background: Previous symptom prevalence studies show a broad spec-

trum of symptoms of varying intensity in patients being just diagnosed

with incurable cancer. It is unclear, though, how physical symptoms and

psychosocial distress should be recorded in order to determine the indi-

vidual need for palliative care.

Methods: We performed a randomized controlled longitudinal cohort

study comparing two dierent strategies for detecting symptoms and needs

of patients with newly diagnosed incurable cancer, determining the eects

on the further course of the disease: a low-threshold repeated screening

using NCCN Distress ermometer and iPOS, versus a comprehensive,

multidimensional assessment using FACT-G and its entity-specic scales,

PHQ4, SCNS-34-SF, iPOS and NCCN Distress ermometer. Primary

study endpoint was the quality of life aer 6 months, as determined by the

same assessment tools. Secondary study endpoints were the amount of

hospital days and the utilization of palliative care, emergency structures,

and psychosocial support.

Result: 504 patients from 34 study centers of the APM study network were

recruited (233 female, 271 male; mean age 66.6 (29 to 90) years). 207 par-

ticipants did not complete the 6 months observation period. Final results

are currently being analyzed and will be presented.

Discussion: e study sheds light on how physical symptoms and psycho-

social distress are best recorded in order to provide individually tailored,

early palliative care, in a cohort of patients known to suer from a variable

symptom spectrum.

Conclusion: e study results will add to the implementation of a struc-

tured supportive approach to incurably aected patients, and to the avoid-

ance of overuse, underuse and misuse of care in this highly relevant and

resource-intensive medical eld.

Disclosure Statement: e authors declare the following:

e study was funded by Innovationsfonds

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts198

Poster

Prediction of the survival time of palliative penile cancer

patients using clinical and laboratory prognostic parameters

and tools

Desiree Louise Dräger; Woehl Maria; Julia Nolting; Sophie Groh;

TimBuchholz; Oliver Hakenberg

Klinik und Poliklinik für Urologie, Universitätsmedizin Rostock, Rostock

Purpose: Making a prognosis is a very challenging and ethically sensi-

tive topic. e clinical impression oen leads to misjudgments. In most

cases, the remaining lifetime is assessed too optimistically and thus over-

estimated by up to 5 times. e prognosis of metastatic penile cancer in

the presence of distant metastases with a 5-year survival of less than 5% is

poor. e aim of the study was to evaluate prognostic tools with clinical

and laboratory parameters as well as potentially new predictors for the

survival time in palliative penile cancer patients.

Material: As part of a prospective monocentric follow-up study on pal-

liative tumor patients (n=23), clinical and laboratory parameters were

recorded, which were correlated with the remaining lifetime using the

univariate and multivariate Cox regression.

Results: e inammation parameters leukocytes (p=0.001), CrP

(p=0.001), albumin (p<0.001) and IL-6 (p<0.001) are signicantly

associated with survival time. Cystatin-C (p=0.014) and LDH (p=0.70)

also correlate signicantly with lifetime. Prognostic tools (KPS (p=0.012),

ECOG (p=0.001), PPI (p<0.001), PaP-S (p=0.001), GPS (p<0.001)) pro-

vide just as precise information.

Discussion: Prognosis assessment is essential for medical and personal

decisions. Although forecast gauges make accurate predictions, they are

rarely used.

Conclusions: Leukocytes, CrP, LDH and albumin have established

themselves as predictors of prognosis. Cystatin-C is also associated with

increased mortality and has not yet been part of a prognostic tool, but

could represent a suitable alternative.

Disclosure Statement: e authors declare no conict of interest.

Virtuelle Realität in der Palliativmedizin

Anja Flier1, Nancy Kuhn-Friedrich1, Dagmar Rolo1, Wolfgang Schütte1

1Halle (Saale), Krankenhaus Martha-Maria Halle-Dölau, Innere Klinik 2/

Palliativstation, Halle (Saale), Deutschland

Background: Die Implementierung der virtuellen Realität im DKG- zer-

tizierten LKZ, in der Klinik für Palliativmedizin, zur Angstreduktion

und zur Beruhigung bei innerer Unruhe bei Patienten in palliativmediz-

inischer Behandlung wird vorgestellt. In einer retrospektiven Erhebung,

von 2018 bis 2020, wurden 50 Patienten mit einem Bronchialkarzinom im

Endstadium analysiert.

Methods: Um die subjektive Einstellung bei dem Symptom der inneren

Unruhe und Angst messen zu können wurde als Messinstrument die

numerische Analogskala (NAS = 0-keine, 1-leichte, 2-mittlere, 3-starke

Belastung) als Scoring-System verwendet. Die Erhebung erfolgte in zwei

Gruppen mit jeweils 25 Patienten. Beide Gruppen erhielten standardis-

ierte erapieoptionen inkl. Respectare, die 2. Gruppe erhielt zusätzlich

die VR-Brille.

Result: In Gruppe 1 betrug der Anteil, die eine Verbesserung durch

standardisierte Optionen erzielen konnte, 71 %, bei der 2. Gruppe, unter

kombinierter Verwendung der VR-Brille, 89 %. Eine Verbesserung

von 1 oder mehr Punktwerten (NAS) konnten 85 % mit Verwendung

VR erlangen, wobei in der zweiten standardisierten Gruppe lediglich 49

% eine Verbesserung von 1 oder mehr Punktwerten erzielen konnten.

Beide Gruppen gingen mit einer Gesamtheit von 55,5 Punktwerten in die

Analyse ein. Nach Beendigung konnte in der 1. Gruppe 29 Punktwerte

und in der 2. Gruppe 37 Punktwerte erhoben werden

Discussion: Dies lässt erkennen, dass die Gruppe mit VR-Brille, mit doch

18 Prozentpunkten eine höhere Einwirkung auf die Symptomlast zeigt,

als die Gruppe mit standardisierten Optionen. Jedoch scheint Respectare

einen nachhaltigeren Einuss auf die Symptomlast zu haben.

Conclusion: Schlussfolgernd ist zu sagen, dass die Kombination der stan-

dardisierten erapieoptionen, die Berührung in Form von Respectare

und dem Angebot der VR Brille einen positiven Einuss auf die

Symptomlast hat. Demnach zeigt sich, dass moderne Technik kombiniert

mit menschlicher Zuwendung und respektvoller Berührung ein Gewinn

für die Patienten sein kann.

Disclosure Statement: e authors declare no conict of interest.

134

Predicting unplanned hospital readmission in palliative

outpatients (PRePP) – study protocol of a longitudinal,

prospective study to identify family caregiver-related and

structural predictors

Leopold Hentschel1,2; André Wellesen3; Luisa Christin Krause4;

Maria von Havranek4; Veronika Greiner4; Christiane Neumann-Stern4;

Michael Kramer5; Beate Hornemann1; Martin Bornhäuser5,6;

Ulrich Schuler2; Katharina Schütte4

1Nationales Centrum für Tumorerkrankungen (NCT/UCC), Universitätsklinikum

Carl Gustav Carus, Psychoonkologischer Dienst, Dresden, Deutschland

2Universitäts PalliativCentrum, Universitätsklinikum Carl Gustav Carus, Dresden,

Deutschland

3Nationales Centrum für Tumorerkrankungen (NCT/UCC), Universitätsklinikum

Carl Gustav Carus, Core Unit Patient-Reported Outcomes, Dresden, Deutschland

4Universitäts PalliativCentrum, Universitätsklinikum Carl Gustav Carus,

Spezialisierte Ambulante Palliativversorgung, Dresden, Deutschland

5Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus,

Dresden, Deutschland

6Nationales Centrum für Tumorerkrankungen (NCT/UCC), Universitätsklinikum

Carl Gustav Carus, Dresden, Deutschland

Background: Specialized outpatient palliative care aims to provide su-

cient end-of-life care, thereby alleviating symptoms and enable incurably

ill patients to stay at home till death. 52% - 94% of Germans desire to die

at home 12008. Relatives of these deceased persons were interviewed by a

written survey. Results: Aer removing duplicates, 4967 questionnaires

were sent out, 3832 delivered, and 1378 completed, yielding a response

rate of 36.0%. Regarding the deceased, 93.8% wanted to die at home, 0.7%

in a hospital, 2.8% in palliative care, 2.4% in a nursing home, and 0.3%

elsewhere. e gures for the relatives were 80.7%, 4.3%, 7.5%, 7.1%, and

0.5%, respectively. Of the deceased 58.9% and of the relatives 59.1% had

their wish fullled. Logistic regression analysis revealed that living in a

rural municipality (adjusted odds ratio [aOR]: 1.88; 95% condence inter-

val [CI]: 1.02-3.43 while actual place of death was home in less than one

third 2be it at a hospital, in a nursing home or at home (with/or without

home care. Unplanned hospital admissions (UHAs) contribute to this dis-

cordance and occur due to various reasons. PRePP aims to explore the

impact of informal caregivers’ (ICs) burden and characteristic of profes-

sional support as predictors for UHAs.

Methods: Starting in 04/21, PRePP is a prospective, observational, lon-

gitudinal, single-arm study to identify structural and ICs related factors.

PRePP uses standardized measures to assess ICs’ quality of life, psycho-

logical distress, anxiety, depression (WHOQOL BREF, NCCN Distress

ermometer, GAD-7, PHQ-9). Furthermore, characteristics of profes-

sional support-network and symptoms are assessed.

Result: In 02/22 the recruitment of 250 patients (sex: 41% f, 59%m; age:

mean=73, SD=13.8) was completed. A preliminary, descriptive partial

analysis of T1 showed the following results: 61% had a participating IC

(sex: 78% f, 22% m; age: mean=65, SD=14.8). Results of the WHOQOL

suggest an average quality of life for ICs. However, ICs are most likely

to experience restrictions on this through negative aect and insucient

opportunities for leisure activities.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 199

Discussion: As this study applies an explorative mono-centric design,

its results will be of preliminary character. Based on the partial results,

we suspect an underrepresentation of highly burdened ICs as they might

refrain from participation.

Conclusions: PRePP supplements scarce knowledge in predicting UHAs

to develop clinical screening tools for UHAs.

References:

1. Escobar Pinzon, L. C. et al. Preference for place of death in Germany.

J. Palliat. Med. 14, 1097–1103 (2011).

2. Sauer, S., Müller, R. & Rothgang, H. Institutionalised dying in

Germany: Trends in place of death distribution: home, hospitals and

nursing homes. Z. Gerontol. Geriatr. 48, 169–175 (2015).

Disclosure Statement: e authors declare no conict of interest.

167

Digitalisierung am Lebensende: Potentiale und Akzeptanz

von Informations- und Kommunikationstechnologie in der

Palliativversorgung (DigiPall) - Zwischenergebnisse

Felix Muehlensiepen1; Anne Gehlhaar1; Felizitas Linderkamp1; Susann

May1; Dunja Bruch1; Kerstin Stahlhut2; Martin Heinze1,2

1Medizinische Hochschule Brandenburg Theodor Fontane, Neuruppin,

Deutschland

2Immanuel Klinik Rüdersdorf, Rüdersdorf bei Berlin, Deutschland

Background: Information and communication technologies (ICT) are

considered an opportunity to support palliative care (PC). e eective-

ness of ICT in PC delivery has only been demonstrated to a limited extent.

e aim of this study is to investigate the use of ICT in PC using a qualita-

tive study design and thus to create a theoretical basis for the development

of a research agenda.

Methods: To explore this domain, telephone-based guided interviews are

conducted with a heterogeneous sample health care practitioners (HCP)

in PC (n≈19). e interviews are analysed using Kuckartz’s structuring

content analysis, supported by MAXQDA.

Result: ICT is used to varying degrees in the dierent settings of PC.

Providers perceive the use of ICT as complementary. ICT enables the

support of work processes, which can relieve the providers’ time. ICT

supports and intensies communication between providers as well as

between providers and patients and their caregivers. In doing so, it reduces

information losses. ICT can increase the quality of care and strengthen

patient-centred care by connecting health care professions/institutions

respectively the use of diagnostic and therapeutic options. e use of ICT

can lead to security risks. Technical decits or insucient user competen-

cies can lead to ineciencies in the care process. ICT impairs communi-

cation, with the result that the multidimensionality of PC is not ensured

by exclusive ICT based care.

Discussion: In order to use ICT eectively in PC, the context factors

under which digital communication takes place and the acceptance of the

users, also including the perspective of patients and their relatives, require

in-depth investigation. Participatory research and development of ICT

might add signicant value to end-of-life care provision.

Conclusion: ICT is perceived by providers as an important support to PA

and is therefore used in many ways. ICT can complement, but not replace,

direct physical contact with patients and their families.

Disclosure Statement: e authors declare no conict of interest.

497

Eect of early palliative care on the distress of oncological

patients with high symptomatic burden, a prospective pilot

study

Anja Thronicke1,2; Philipp von Trott3; Friedemann Schad1,3

1Forschungsinstitut Havelhöhe gGmbH am Gemeinschaftskrankenhaus

Havelhöhe, Berlin, Deutschland , Berlin, Deutschland

2Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Charité–

Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and

Humboldt-Universität zu Berlin, Berlin, Deutschland

3Interdisziplinäre Onkologie und Palliativmedizin, Gemeinschaftskrankenhaus

Havelhöhe, Berlin, Deutschland

Background: Oncological patients with high symptomatic burden suer

from psychological and physiological constraints during end-of-life care.

Early palliative care (ePC) has been shown to signicantly improve the

quality of life of oncological patients and may lead to longer survival (1).

e objective of this study is to compare the distress of high symptomatic

burdened oncological patients before and aer inpatient ePC.

Methods: 38 stage I-IV oncological patients with self-reporting of ≥ 5

points on the NCCN Distress ermometer scale (2) are included. e

primary endpoint is the improvement of self-reported distress by 2 points

(NCCN Distress ermometer) 12±2 days aer the start of ePC. e sec-

ondary endpoints are the evaluation of distress, symptom intensity, over-

all and progression free survival and complication rate. e applied ePC

consists of guideline-oriented symptom management, elaborate consul-

tation life review (3), complementary medication and non-pharmacolog-

ical applications. e statistical analyses will be performed descriptively.

Study’s registration number: DRKS00013335.

Result: 20 of 38 oncological patients have already been included in the

study. It is anticipated that patient’s distress as a measurement of anxiety

and depressive symptoms will improve 12±2 days aer the start of inpa-

tient ePC.

Discussion: First results will be shown and discussed.

Conclusions: It is expected that patient’s symptomatic burden will be

reduced by the application of ePC in the presented study. Meanwhile, a

multicenter study is being prepared and participating palliative care cen-

ters are invited.

Indication of source:

1 Temel JS et al. New England Journal of Medicine 2010

2 Mitchell AJ et al. J Clin Oncol 2017

3 ronicke A et al. Complement Med Res 2018

Disclosure Statement: FS reports grants from AstraZeneca, Abnoba GmbH,

Iscador AG, and Helixor Heilmittel GmbH outside the submitted work. e other

authors declare no conict of interest.

634

Dying in Hospitals – Optimization of care in the dying phase

(StiK-OV) – Results of an online survey

Sukhvir Kaur1; Karin Oechsle2; Holger Schulz3; Kathleen Boström1;

Nikolas Oubaid2; Christina Plathe-Ignatz2; Anneke Ullrich2;

Raymond Voltz1; Kerstin Kremeike1

1University of Cologne, Faculty of Medicine and University Hospital Cologne,

Department of Palliative Medicine, Köln, Deutschland

2Palliative Care Unit, Department of Oncology, Hematology and BMT, University

Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

3Department of Medical Psychology, University Hospital Hamburg-Eppendorf,

Hamburg, Deutschland

Background: Hospitals are the most frequent place of death in Germany

(47%), but at the same time, the least preferred one – for both patients and

their relatives. To optimize care in the dying phase by using a bottom-up

approach, the StiK-OV project aims to implement and evaluate specic

measures on dierent non-palliative wards at two university hospitals. In

the rst phase of the project, we assess the current state of care in the dying

phase on dierent wards.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts200

Methods: We conducted an online survey with national health care pro-

fessionals consisting of seven open questions on important aspects, facili-

tators, barriers and needs for improvement as well as Covid-19 pandemic

specics regarding care in the dying phase. Qualitative data was analyzed

thematically.

Result: Of 67 participants, 66% work in clinical practice as nursing sta

(52%) and physicians (30%) and 34% in management or administration.

As relevant topics of care in the dying phase, we identied involvement of

relatives, symptom control, patient-centeredness, professional competen-

cies, as well as time, space and human resources. Participants state a need

for improvement regarding these topics. During the pandemic, involve-

ment of relatives and patient-centeredness were dicult to maintain due

to visiting restrictions and higher workload, resulting in patient isolation

and dying in loneliness.

Discussion: e survey revealed common topics of importance which

should be targeted by ward-specic measures. Diculties due to the pan-

demic have to be accounted for to achieve optimal care in the dying phase

under exceptional circumstances.

Conclusion: e survey gave insights on care in the dying phase from

the perspective of health care professionals that can help to develop and

implement situation-specic measures to signicantly improve the quality

of care during the dying phase in hospitals. A bottom-up approach aims to

increase the sta motivation to implement respective measures.

Disclosure Statement: e authors declare no conict of interest.

855

Percutaneous Endoscopic Gastrostomy for palliative therapy

in oncological patients – the safety of a vulnerable cohort in a

large retrospective, monocentre Charité study

Tobias Kinzel1; Viktoria Reich1; Leonie Schuhmacher1; Christian Bojarski1;

Andreas Adler2; Wilfried Veltzke-Schlieker2; Christian Jürgensen2;

Bertram Wiedenmann2; Britta Siegmund1; Federica Branchi1;

Juliane Buchkremer1; Christoph Treese1

1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology,

Infectious Diseases and Rheumatology (including Nutrition Medicine), Berlin,

Deutschland

2Charité – Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt-Universität zu Berlin, Department of Hepatology and

Gastroenterology, Berlin, Germany, Berlin, Deutschland

Background: Especially oncological patients, whose conditions require

palliative care, are part of the daily ethical discussion in every clinic. e

benets of an intervention like the PEG-Insertion must be carefully eval-

uated. In this analysis, we focussed on the safety prole regarding the per-

formance status and the three dierent PEG-insertion techniques.

Methods: e cohort of patients in palliative care with an oncological

diagnosis is a subgroup based on a large retrospective database of patients,

receiving a new PEG between January 2016 and December 2021 in the

three endoscopic centers of the Charité-Universitätsmedizin Berlin. To

investigate the safety prole of PEG in this subgroup we did uni- and mul-

tivariate analyses.

Result: 146 patients with oncological diagnosis and PEG-insertion within

the context of palliative therapy were included and compared with 1424

patients. Neither the performance status (ECOG 1/2 und ECOG 3/4;

p=0.117) nor in comparison to the whole cohort (p=0.961) dierences

regarding major complications were evaluated. e gastropexy-tech-

niques (direct puncture and Hybrid) demonstrated its benet compared

to the pull-through method in the cohort with other diagnoses (p<0.001),

while the results in the subgroup just pointed out a tendency (Gastropexy

2.1; pull-through 9.8%).

Discussion: e study is mostly limited by its retrospective design and

especially the small number of patients with major complications in the

subgroup.

Conclusion: Despite the necessity of a strict following of the indications we

assume that PEG-insertion for palliative therapy in oncological patients is

as safe as it is for other cohorts and that the safety prole of the procedure

is independent of the performance status. Furthermore, our data suggest

even in this special cohort a benet for both gastropexy-techniques.

Disclosure Statement: e authors declare no conict of interest.

1023

Standardized screening for palliative care needs on elective

admission to in-patient oncological unit

Astrid Schnabel1; Kathrin Reetz2; Nicole Wegener3; Eva-Maria Balsen2;

Florian Lordick1; Sven Bercker3

1Universitätsklinikum Leipzig, Klinik und Poliklinik für Onkologie,

Gastroenterologie, Hepatologie, Pneumologie und Infektologie, Leipzig,

Deutschland

2Universitätsklinikum Leipzig, Klinik und Poliklinik für Onkologie,

Gastroenterologie, Hepatologie, Pneumologie und Infektologie,

Patientenmanagment, Leipzig, Deutschland

3Universitätsklinikum Leipzig, Klinik für Anästhesiologie und Intensivmedizin,

Leipzig, Deutschland

Standardized screening for palliative care needs on elective

admission to in-patient oncological unit

Background: While implementing the national cancer certication pro-

gram for oncological and comprehensive cancer centres we collected and

analysed data prospectively for quality assurance.

Methods: Screening was conducted pencil-paper-based using the vali-

dated new Minimal Documentation System (MIDOS²) and the Distress

ermometer (DT) for self-assessment for physical symptoms and psy-

chosocial distress of cancer patients. MIDOS² sum score >4 or a DT score

>4 was dened as positive for palliative care needs assessment. In these

cases, an automatic referral to the specialist in-patient palliative care ser-

vice was triggered. Subsequently, either specialist palliative care or coun-

selling for general palliative care was applied.

Results: In 2021, 139 cancer patients had been electively admitted to

our oncological unit. All but two of these patients underwent the above

screening process. e response rate was 91% (n=125). Out of these 125

cases, 65 patients (52%) were screened positive for palliative care needs

assessment. Of these, in 60 cases (92%) an automatic referral to the spe-

cialist in-patient palliative care service was triggered. Finally, in 35 cases

the palliative care needs assessment was performed. Out of these, 23 cases

(66%) received general palliative care counselling, and 12 cases (34%) spe-

cialist palliative care. Screening identied 9% of electively admitted cases

as in need for specialist palliative care.

Conclusion: It is possible to integrate a standardized screening for pal-

liative care needs on planned clinical routine admission to oncological

in-patient units. As such, this screening is able to complement the a priori

referral to specialist in-patient palliative care service, by that contributing

to comprehensive oncological care.

Disclosure Statement: e authors declare the following:

Vortragshonoraria DGK

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 201

Psychooncology

Best-of-Abstract-Vortrag

359

Distress in hospitalized cancer patients: Associations

with personality traits, clinical and psychosocial

characteristics

Theresia Pichler1; Birgitt Marten-Mittag2; Kerstin Hermelink3;

Eva Telzerow4; Tamara Frank1,2; Ulrike Ackermann5; Claus Belka6;

Stephanie E. Combs7,8,9; Christian Gratzke10,11; Jürgen Gschwend12;

Nadia Harbeck3,13; Volker Heinemann1,4; Kathleen Herkommer12;

Marion Kiechle5; Sven Mahner3; Ste Pigorsch14; Josene Rauch6;

Christian-Georg Stief11; Friederike Mumm1,4; Pia Heußner4,15;

Peter Herschbach2; Andreas Dinkel2

1Comprehensive Cancer Center Munich, Munich, Deutschland

2Technical University of Munich, School of Medicine, Klinikum rechts der

Isar, Department of Psychosomatic Medicine and Psychotherapy, Munich,

Deutschland

3Department of Obstetrics and Gynecology, University Hospital, LMU Munich,

Munich, Deutschland

4Department of Internal Medicine III, University Hospital, LMU Munich, Munich,

Deutschland

5Technical University of Munich, School of Medicine, Klinikum rechts der Isar,

Department of Gynaecology and Obstetrics, Munich, Deutschland

6Department of Radiation Oncology, University Hospital, LMU Munich, Munich,

Deutschland

7Helmholtz Zentrum München (HMGU), Department of Radiation Medicine,

Oberschleißheim, Deutschland

8Deutsches Konsortium für Translationale Krebsforschung (DKTZ), partner site

Munich, Deutschland

9Technical University of Munich, School of Medicine, Klinikum rechts der Isar,

Department of Radiation Oncology, Munich, Deutschland

10Department of Urology, University Hospital of Freiburg, Freiburg, Deutschland

11Department of Urology, University Hospital, LMU Munich, Munich,

Deutschland

12Technical University of Munich, School of Medicine, Klinikum rechts der Isar,

Department of Urology, Munich, Deutschland

13Breast Center, University Hospital, LMU Munich, Munich, Deutschland

14Technical University of Munich, School of Medicine, Klinikum rechts der Isar,

Department of Radiation Oncology, Munich, Deutschland

15Cancer Center Oberland, Garmisch-Partenkirchen General Hospital, Garmisch-

Partenkirchen, Deutschland

Background: Identication of psychosocial distress and associated deter-

minants is important for allocation and supply of patient-oriented psy-

cho-oncological support. is study investigated the associations between

dispositional characteristics and current clinical and psychosocial deter-

minants of distress in hospitalized cancer patients.

Methods: e cross-sectional study investigated 879 inpatients with dif-

ferent cancer sites treated in the Comprehensive Cancer Center Munich.

Assessment of determinants of elevated distress comprised sociodemo-

graphic, clinical and psychosocial characteristics as well as dimensions of

personality. We calculated a multiple linear regression to identify determi-

nants of psychosocial distress.

Result: Overall, 46.2% (n = 406) of the participants reported clinically

signicant distress. Results of the multiple linear regression model showed

that younger age, higher neuroticism, having metastases, being in a worse

physical condition, depressive symptoms, not feeling well informed about

psychological support and previous psychological treatment were signi-

cantly associated with higher psychosocial distress.

Discussion: Psychosocial distress of cancer patients is associated with

dispositional vulnerability, i.e. neuroticism, as well as current clinical and

psychosocial characteristics.

Conclusion: Health care professionals should consider both, the more

transient emotional responses, such as depressive symptoms, as well as

more enduring patient characteristics, like neuroticism.

Indication of source

Pichler T, Dinkel A, et al. Distress in hospitalized cancer patients:

Associations with personality traits, clinical and psychosocial characteris-

tics. Psychooncology. 2019;28(10):2049-59. (submitted)

Pichler T, Dinkel A, et al. Distress bei stationären Krebspatienten:

Zusammenhänge mit Persönlichkeitsmerkmalen, klinischen und psycho-

sozialen Determinanten. (submitted to 19. PSO-Jahrestagung)

Disclosure Statement: e authors declare no conict of interest.

871

Open the door for parental themes. The development and

evaluation of an intervention for healthcare professionals on

parenthood and cancer. A randomized controlled pilot-study

Lene Marie Johannsen1; Wiebke Frerichs1; Laura Inhestern1; Rebecca

Philipp1; Corinna Bergelt1,2

1Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum

Hamburg-Eppendorf, Hamburg, Deutschland

2Institut für Medizinische Psychologie, Universitätsmedizin Greifswald,

Greifswald, Deutschland

Cancer patients with minor children face specic burden and support

needs, which are oen not adequately addressed by their healthcare pro-

fessionals (HCPs). HCPs oen do not proactively ask for child- and fam-

ily-specic themes due to time pressure and structural barriers as well

as lacking knowledge, condence and competencies. erefore, we devel-

oped and pilot-evaluated a 3-hour training on parenthood and cancer.

e study was conducted as a 3-armed randomized controlled pilot-

trial with three measurement points (baseline, post-training, 3-months

follow-up), comparing face-to-face training (F2F), E-Learning (EL) and

waitlist-control group (CG). Intervention eects were analyzed on HCPs’

competency to approach child- and family-related themes, knowledge and

self-ecacy using linear mixed models. Training’s feasibility and accept-

ability were analyzed using descriptive statistics and non-parametric tests.

Study participants (n=152) were mostly female (89%) and psycholo-

gists (38%; physicians 26%; nurses 18%). Main reasons for study partici-

pation were to better address patient’s needs (90%), to better understand

aected parents and to gain knowledge (55% each). Participants of F2F

and EL were both highly satised with the training. Analyses indicated

positive intervention eects as F2F and EL showed stronger improve-

ments in knowledge and self-ecacy than CG.

Findings demonstrate positive eects of the interdisciplinary train-

ing for both F2F and EL intervention. Since enrollment rates were lower

among physicians and nurses than among psychologists, future imple-

mentation eorts should specically address and encourage those profes-

sions to participate.

Findings show positive intervention eects and indicate training being

an adequate approach to increase HCPs’ knowledge and competencies to

improve their abilities in caring for parents with cancer.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts202

Poster

Trauma- and stressor-related disorders among survivors of

hematological malignancies

Peter Esser1; Franziska Springer1; Jochen Ernst1; Katharina Kuba1;

Uwe Platzbecker2; Vladan Vucinic2; Anja Mehnert-Theuerkauf1

1Abteilung für Medizinische Psychologie und Medizinische Soziologie,

Universitätsklinikum Leipzig, Deutschland

2Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie,

Universitätsklinikum Leipzig, Leipzig, Deutschland

Background: Trauma- and stressor-related disorders such as posttrau-

matic stress disorder (PTSD) or adjustment disorder (AD) pose a serious

threat for patients with medical conditions. Hematological cancer patients

may face various stressors during their treatment such as stem cell trans-

plantation (SCT) which is associated with multiple distressing events.

Nevertheless, research on the specic types and sources of stressor-related

symptomatology among this patient group is sparse to date.

Methods: Between April 2019 and August 2021, this German cross-sec-

tional study has recruited almost 300 hematological cancer patients,

among which about one half has undergone either autologous or allo-

geneic SCT. Using a structured clinical interview (SCID-5) based on

updated DSM-5 diagnostic criteria, participants are assessed for mental

disorders including PTSD and AD. Descriptive analyses are used to pro-

vide prevalence rates of these disorders and the frequency of disease-re-

lated stressors experienced during treatment.

Result: We will provide results of the rst analyes regarding prevalence

rates of mental disorders including PTSD and AD among both the total

sample and subgroups stratied by treatment (SCT vs. no-SCT) and other

patient characteristics. Analyses will also provide the types and frequency

of disease-related stressors during the disease and treatment trajectory.

Using the updated diagnostic critiera, we will also assess how many and

which type of disease-related stressors reported by the patients meet the

trauma criteria as dened in the DSM-5.

Discussion/Conclusion: Our study will help to inform the health care

system and health care providers about the specic stressor-related bur-

den associated with hematological malignancies and their treatment.

Furthermore, ndings may provide empirical ndings on the question to

which extent the trauma concept may be reasonably applied to this pop-

ulation. ese results will help to establish hypotheses on how treatment

and support programs may be tailored to the specic situation of this

population.

Disclosure Statement: e authors declare no conict of interest.

Training needs and barriers of nursing sta in oncology

regarding psycho-oncological screening

Lara Dreismann; Tanja Zimmermann

Medizinische Hochschule Hannover, Klinik für Psychosomatik und

Psychotherapie, Hannover, Deutschland

Background: Psychooncological care can reduce psychological distress

in cancer patients and increase quality of life. Unfortunately, even with

standardized screening tools, early identication of distressed patients

and indication-based treatment are oen missed. One reason may be per-

sonal barriers on the side of the medical team and ambiguities regarding

the screening process. But what are the barriers for nurses in oncology to

perform psychooncological screening? Is there a need for training on the

topic of psychooncological screening?

Methods: N = 15 semi-structured interviews with nursing experts (n =

10 female, 24-62 years) from the oncology departments of the University

Hospitals of Hannover, Leipzig and Dresden were conducted and ana-

lyzed using qualitative content analysis according to Mayring.

Result: Structural barriers like time pressure and missing focus on psy-

chological distress are present. Hurdles on the side of nurses are primar-

ily lack of knowledge and communication uncertainties. e experts

assume a great interest in training. As far as the framework conditions

are concerned, integration into the working hours and the involvement

of the entire nursing team appear to be essential. e content should be

practical, include information on psychological stress, psycho-oncology,

screening process, communication and self-care as well as key phrases for

everyday work and case examples.

Discussion: Despite guidelines, the screening process and information

about psycho-oncological support is not included in the daily nursing ser-

vice catalogue. In addition, patients’ obstacles to referral for psycho-on-

cology should also be considered.

Conclusion: ere is a clear need for training on psycho-oncology,

screening implementation, and communication to overcome knowledge

decites and uncertainties and to establish an interdisciplinary screening

process.

Disclosure Statement: e authors declare no conict of interest.

Validation of the psychometric properties of a

“Modied Version of the Hornheider Screening Instrument”

(HSI-MV) using a sample of outpatient and inpatient skin

tumor patients

Britta Buchhold1; Stine Lutze2; Jennis Freyer-Adam1; Michael Jünger2;

Claudia Nordt3; Sebastian Peters3; Stephan Kersting3

1Greifswald, University Medicine , Institute for Medical Psychology, Greifswald,

Deutschland

2Greifswald, University Medicine , Dermatology, Greifswald, Deutschland

3Greifswald, University Medicine, Oncology Center, Greifswald, Deutschland

Purpose: e recognition of psychosocial stress is of great importance

in the treatment of oncological patients. In our Oncology Center, a

tumor-unspecic screening instrument was needed to identify outpa-

tients and inpatients with psychosocial care needs. Among the methods

recommended by the German Working Group for Psychooncology, the

Hornheider Screening Instrument (HSI, questionnaire with 7 items)1

seems to meet our requirements. In clinical practice, the HSI represents

a cost-eective, quickly evaluable, and accepted instrument. e 5th HSI

item, “Is anyone in your family particularly burdened by hospitalization?”

is intended to assess the presence of illness-related family burden. But is

this item equally suitable for outpatients and inpatients? is study inves-

tigated how replacing the original item aects the test performance of this

modied version of the HSI and the assessed family burden.

Methods: 92 outpatients and 98 inpatients with skin tumors assessed their

psychosocial situation using dierent questionnaires.

Results: Compared to the outpatients (9,2%), more than twice as many

inpatients (21,8%) answered “yes” to the item. If the question was replaced

by: “Is anyone in your family particularly burdened by your illness or the

course of your illness?” this setting-related dierence was not evident

(21,6% vs. 25,5%).

Discussion: e “Alternative item” and the “Modied version of the HSI”

(HSI-MV) proved to be superior to the original item and the HSI with

regard to all criteria examined. Psychosocially distressed individuals were

identied with a higher accuracy of hits.

Conclusions: e HSI-MV can be used as a reliable and valid instrument

for the systematic assessment of psychosocial care needs in outpatient and

inpatient settings. Depending on Psychosocial care capacity, a threshold

of ≥5 or ≥4 is appropriate. In addition to screening, support needs should

be inquired about.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 203

Reference:

1 Strittmatter G, Mawick R & Tilkorn M. How to identify patients in need of

psychological intervention. Recent Results Cancer Res. 2002; 160: 353-61.

Disclosure Statement: e authors declare no conict of interest.

156

Dealing with fear of cancer recurrence – evaluation of a

psychooncological group therapy program

Marnie Steinecke; Jana Joachims; Marei Kotzerke; Cathérine Lüke;

Janina Berg; Tanja Zimmermann

Klinik für Psychosomatik und Psychotherapie, Medizinische Hochschule

Hannover, Hannover, Deutschland

Background: Fear of cancer recurrence (FCR) is a common burden for

cancer patients. However, it is oen challenging to nd outpatient psy-

chological support. erefore, for the following study, an outpatient group

adapted from Waadt et al.’s manual (2011)1 was developed to focus on spe-

cic needs of oncological patients experiencing FCR.

Methods: e group program consisted of 8 treatment sessions in small-

sized closed groups with 6-8 patients and 2 therapists. e content was

standardized and included behavioral strategies (psychoeducation, cogni-

tive exposure, coping strategies and resources) as well as mindfulness. e

intervention was evaluated by comparing FCR, anxiety and depression

before and aer the group using Wilcoxon-signed-rank-tests.

Result: In total, N = 33 patients with varying oncological diagnoses

participated in the group intervention. Out of these, 26 were female

(76.5%) and 7 were male (20.6%). e mean age was 57.6 years, rang-

ing from 42 to 77 years. A signicant decrease in depression (z=−3.09,

p=.002, n=18), anxiety (z=−3.00, p=.003, n=19) and FCR (z=−2.47,

p = .013, n = 13) was found aer nishing the group intervention.

Moreover, our patients rated the techniques covered in the intervention as

helpful for dealing with FCR and feasible in everyday life.

Discussion: Despite limitations in implementation and recruitment of

patients due to the Corona pandemic, results show positive changes in the

group intervention with respect to FCR, anxiety, and depression.

Conclusion: e results indicate that a structured group therapy program

with a focus on FCR for oncological patients can be an eective and feasi-

ble intervention improving outpatient psychooncological care.

Indication of source:

1 Waadt, S., Duran, G., Berg, P. & Herschbach, P. (2011). Progredienzangst.

Manual zur Behandlung von Zukunsängsten bei chronisch Kranken. Stuttgart:

Schattauer.

Disclosure Statement: e authors declare no conict of interest.

231

Psychological burden after tumor nephrectomy

Marc Heydenreich; Dirk-Henrik Zermann

Vogtland-Klinik Bad Elster, Bad Elster, Deutschland

Background: e diagnosis and therapy of cancer oen results in a psy-

chosocial stress for the aected patient and their families. Holistic reha-

bilitative care includes its evaluation, treatment and psychosocial support.

e aim of the study was to evaluate the psycho-oncological situation of

patients aer nephrectomy.

Methods: 422 patients with an average age of 67.7 years were examined

with the FBK-R23 questionnaire aer nephrectomy at the beginning of a

follow-up rehabilitation.

Result: e data from 422 kidney patients could be evaluated.

Comparison of FBK-values inconspicuous (<34) and noticeable

(>34)– Number of patients who perceived a psychological one-on-one

interview (MW=mean; SD= standard deviation):

• FBK<34=14.2 (8.7) (n=367);

• FBK>34=48.9 (13.4) (n=55);

• psychological one-on-one interview FBK=43.9 (7.6) (n=21)

Comparison of FBK values between men and women:

• FBK (men)=15.9 (14.7) (n=250)

• FBK (women)=21.0 (16.0) (n=172)

Comparison of the FBK values with regard to the decades of age:

• 30-49 years: FBK=22.6 (17.7) (n=19)

• 50-69 years: FBK=19.6 (17.2) (n=221)

• 70-99 years: FBK=15.4 (12.3) (n=182)

Comparison of FBK values between employees and pensioners:

• FBK (employees)=20.4 (16.7) (n=209)

• FBK (pensioners)=15.5 (13.6) (n=213)

Discussion: 13% of the examined patients had abnormal FBK-23 ques-

tionnaire values and thus a signicant need for psycho-oncological treat-

ment. Women and younger / working patients are more oen aected.

Conclusion: Psychosocial treatment oers for patients aer nephrectomy

must be further developed and adapted. In the aercare the physician has

a clear responsibility for the psychosocial care of the patient.

Disclosure Statement: e authors declare no conict of interest.

297

The impact of the COVID-19 pandemic on outpatient cancer

patients

Tamara Frank1,2; Theresia Pichler1; Sabrina Maier1; Ineke Batenhorst1;

Tanja Daltrozzo2; Nadia Harbeck1,3; Hana Algül1; Volker Heinemann1,4;

Kerstin Hermelink5; Andreas Dinkel2; Friederike Mumm1,4

1Comprehensive Cancer Center München, München, Deutschland

2Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,

Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München,

München, Deutschland

3Brustzentrum, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe,

Klinikum der Universität München, LMU München, München, Deutschland

4Medizinische Klinik und Poliklinik III, Klinikum der Universität München, LMU

München, München, Deutschland

5Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der

Universität München, LMU München, München, Deutschland

Background: e COVID-19 pandemic has led to higher levels of stress,

anxiety and depression in the population. Oncological patients might be

particularly vulnerable, since structural changes and limited resources

within medical care might aect treatment. Besides, due to their under-

lying condition, most are at-risk patients. e aim of this study was to

identify the specic stressors and current needs of cancer patients.

Methods: Between 11/2020 and 02/2021 122 outpatient cancer patients of

the Comprehensive Cancer Center Munich participated in the study aer

giving informed consent. Based on a standardized, semi-structured inter-

view, participants were asked about their knowledge and concerns about

COVID-19, risk perception, condence in the national health system

and readiness to get vaccinated against COVID-19. Psychosocial distress,

symptoms of anxiety and depression, somatic symptoms and self-ecacy

were collected via standardized questionnaires. Additionally, socio-demo-

graphic and medical data were collected.

Result: More than a third of the patients (34.2%, n = 41) require addi-

tional information about the eects of the coronavirus on their cancer

and/or treatment. Patients most oen mentioned unanswered questions

regarding the impact of a COVID-19- infection on cancer, followed by

vaccination and treatment. About 17% had faced changes concerning

their current or planned treatment. 34.7% (n=42) of the patients were

signicantly distressed (mean distress score: 3.7; scale: 0-10). A possi-

ble overload of the health care system was the most commonly reported,

COVID-related fear (77.9%).

Discussion: Findings suggest that oncologists should educate and support

patients by exploring and responding to their diverse questions regarding

the eect of COVID-19 on their disease and treatment.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts204

Conclusion: Providing emotional support and oering reliable sources of

information can help cancer patients navigate through uncertainties and

reduce anxiety.

Presented at: IPOS 2021, DKPM 2021, DGHO 2021, PSO 2021

Disclosure Statement: e authors declare no conict of interest.

313

Do cancer patients benet from talking to cancer survivors?

Lessons learned from the German integrated, cross-sectoral

psycho-oncology programme (isPO)

Vera Schiewer1; Anne Klein1; Hildegard Labouvie1; Hedy Kerek-Bodden2;

Michael Kusch1

1Klinik I für Innere Medzin, Universitätsklinikum Köln, Klinische

Psychoonkologie/ Versorgungsforschung, Köln, Deutschland

2Haus der Krebs-Selbsthilfe - Bundesverband e.V., Bonn, Deutschland

Background: e project isPO, integrated cross-sectoral psycho-on-

cology, funded by the innovation fund at the G-BA, is investigating the

quality of the stepped-care-programme isPO. As part of the programme,

long-term cancer survivors (isPO-Oncoguides) inform cancer patients

undergoing active treatment about psychosocial aspects of cancer in a

timely and personal manner. e quality and helpfulness of these patient

information conversations has not been investigated so far.

Methods: Long-term cancer survivors were qualied and certied as

so-called isPO-Oncoguides (OG) by the German Cancer Self-Help

Association. To assess the quality and helpfulness of the personal conver-

sation of the patient and the OG, evaluation sheets are used. e sheets

are completed by the OG immediately aer the conversation and by the

patient within 1 to 3 months. e evaluation sheet consists of two ques-

tions on the quality of the conversation: a) the appropriateness of the

timing of the contact, b) the degree of condence conveyed and two ques-

tions on the helpfulness of the conversation: a) helpfulness for orientation

regarding cancer and b) perceived support in coping with cancer.

Result: So far 340 OGs and 220 patients completed the evaluation sheet.

Preliminary analyses show that 92% of the patients and 70% of the OG

answered at least one of the four questions. e assessment of the personal

contact and conversation is predominantly rated as positive by both the

patients and the OGs. Analyses of the concordance of OG and patient

assessment reveal discrepancies, especially when patients rate the quality

and helpfulness of the conversation with OG’s negatively.

Discussion: e presentation will discuss the ndings of the benets of

conversations between patients with cancer and long-term cancer survi-

vors in the early stages of cancer therapy.

Conclusion: Cancer patients in active treatment benet from the personal

contact and conversation with long-term cancer survivors.

Disclosure Statement: e authors declare no conict of interest.

324

The eect of eHealth interventions on psychosocial distress,

coping strategies, quality of life and unmet supportive care

needs among cancer patients during acute treatment stage.

A rapid review

Miriam Grapp1; Senta Kiermeier1; Karin Jordan2;

Hans-Christoph Friederich3; Imad Maatouk1

1Universitätsklinik Heidelberg, Klinik für Allgemeine Innere Medizin und

Psychosomatik, Psychoonkologische Ambulanz am NCT, Heidelberg,

Deutschland

2Universitätsklinik Heidelberg, Abteilung Innere Medizin V, Hämatologie,

Onkologie und Rheumatologie, Heidelberg, Deutschland

3Universitätsklinik Heidelberg, Klinik für Allgemeine Innere Medizin und

Psychosomatik, Heidelberg, Deutschland

Background: In recent years, an increasing number of eHealth interven-

tions have been developed for cancer patients under anticancer treat-

ment. Few reviews already exist in this eld, focusing mainly on symptom

tracking and symptom management. erefore, we conducted a rapid

review of the impact of eHealth interventions on psychological distress

(general distress, depression, anxiety), coping strategies, quality of life

(QoL) and unmet psychosocial care needs among cancer patients during

treatment.

Methods: e review followed the reporting guidelines outlined in the

PRISMA statement and was registered at the International Prospective

MEDLINE, PsycINFO and PSYNDEX were systematically searched.

Included were randomized controlled trials (RCTs), reviews and

meta-analyses.

Result: A total of 28 studies which met the eligibility criteria – 10 system-

atic reviews and 18 randomized clinical trials – were considered for this

rapid review. e included studies were published from 2011-2020, with

21 of 28 studies being from 2018 or later. Both reviews and RCTs showed

a high degree of heterogeneity regarding type of intervention, character-

istics of the target population (tumor entity, time since diagnosis, type of

treatment), and outcomes used.

Discussion: Overall, the evidence is encouraging, but limited. ere are

partial positive eects, especially for quality of life, depression and anxiety.

However, due to the observed heterogeneity and methodological prob-

lems of the individual studies, no clear evidence can be derived.

Conclusion: eHealth interventions seem to have great potential to

improve psychological distress, especially in patients that are otherwise

underserved. In order to improve the quality and strength of current

research guidelines/recommendations are urgently needed for both the

development of eHealth interventions and their evaluation.

Disclosure Statement: e authors declare no conict of interest.

360

Screening and psycho-oncological support in patients with

head and neck cancer and brain malignancies before radiation

with mask xation: a feasibility study of a multidisciplinary

care program

Sebastian Adeberg1; Christina Sauer2; Sebastian Regnery1; Paul Windisch1;

Christoph Nikendei2; Johannes Ehrenthal2; Rami El Shae1,3;

Juliane Hörner-Rieber1; Laila König1; Sati Akbaba4; Kristin Lang1;

Thomas Held1; Karim Zaoui5; Julius Moratin6; Christian Freudlsperger6;

Stefan Rieken1,3; Jürgen Peter Debus1; Hans-Christoph Friederich2;

Imad Maatouk2

1Heidelberg, University Hospital Heidelberg , Department of Radiation

Oncology, Heidelberg, Deutschland

2Heidelberg, University Hospital Heidelberg , Department of General Internal

Medicine and Psychosomatics, Heidelberg, Deutschland

3University Hospital Göttingen, Department of Radiation Oncology, Göttingen,

Deutschland

4Mainz, University Hospital Mainz, Department of Radiation Oncology, Mainz,

Deutschland

5Heidelberg, University Hospital Heidelberg, Department of

Otorhinolaryngology, Head and Neck Surgery, Heidelberg, Deutschland

6Heidelberg, University Hospital Heidelberg, Department of Oral and

Maxillofacial Surgery, Heidelberg, Deutschland

e present single-center, single-arm trial investigates the feasibility of a

multidisciplinary care program, which aims to reduce psychological dis-

tress and to improve compliance in patients with head and neck cancer

or brain malignancies undergoing radiotherapy with mask-xation. Our

care program comprised (1) a screening and (2) the provision of a psy-

cho-oncological intervention using imaginative stabilization techniques

for distressed patients and/or in case of subjective needs. Physicians could

also directly assign patients to the intervention. Of the n = 1020 screened

patients, n = 257 patients indicated a distress ≥ 5, and n = 141 patients

reported panic attacks. 25% of asked patients reported a subjective inter-

est in psycho-oncological support. In sum, 35 patients received the psy-

cho-oncological intervention, whereof 74% were assigned by radiation

oncologists. In this small patient cohort no signicant pre-post eects of

the intervention could be detected. Our results indicate good feasibility

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 205

of a multidisciplinary care program for patients before radiotherapy with

mask-xations. e screening results underline the high psychological

distress and demand of psycho-oncological support. However, as the

utilization of our intervention was low, future studies should investigate

barriers and improve compliance for psycho-oncological services in these

patients.

Disclosure Statement: e authors declare no conict of interest.

386

Eectiveness of a Video Sequence based Intervention on

Anxiety, Fatigue and Depression in Cancer Patients

Elisabeth Jentschke; Sven Neubert; Sina Schlecht; Antonia Rabe

Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,

Psychoonkologie , Würzburg, Deutschland

Background: Many cancer patients suer from psychological problems,

most notably anxiety and depression1 as well as cancer-related fatigue2.

e COVID-19 pandemic may further worsen mental health3 and com-

plicate psycho-oncological care. is study examines the short- and

long-term eects of a video intervention, including psychoeducation and

practical exercises on anxiety, depression and fatigue.

Methods: Participants will be randomly assigned to an intervention

group, receiving the video intervention rst or a control group, receiv-

ing it subsequently. e intervention lasts four weeks and is structured in

eight video sequences. Anxiety, depression, and fatigue are measured by

validated questionnaires at three measurement points (before and aer

the intervention, 3 months aer the end of the intervention).e control

group receives an additional questionnaire at the beginning of the waiting

period.

Result: 172 patients (86 per group) with mixed cancer diagnoses were

included in the study. e study is recently conducted. It is expected that

cancer patients who participate in the video intervention will experience a

decrease in symptoms or at least no worsening.

Discussion: Oering and evaluating the eects of digital interventions

seems all the more relevant during the COVID-19 pandemic. With the

pandemic inuencing mental health issues, the validity of the outcomes

may be limited.

Conclusion: If the video sequence based intervention could reduce anxi-

ety, depression and fatigue, this type of therapy could expand psycho-on-

cological care.

References:

1 Kuhnt S et al.Twelve-Month and Lifetime Prevalence ofMental Disorders

in Cancer Patients. Psychother Psychosom.2016;85(5):289-96.

2 Mehnert A et al. One in two cancer patients is signicantly dis-

tressed: Prevalence and indicators of distress. Psychooncology. 2018

Jan;27(1):75-82.

3 Torales J, O’Higgins M, Castaldelli-Maia JM, Ventriglio A. e out-

break of COVID-19 coronavirus and its impact on global mental

health. Int J Soc Psychiatry. 2020;66(4):317-320.

Disclosure Statement: e authors declare no conict of interest.

485

The Yinota-trial: Ecacy of Yoga-intervention in high grade

glioma patients and their caregivers – patient-reported

outcomes and serum stress parameters

Elisabeth Jentschke1; Antonia Rabe1; Carsten Hagemann2; Jörg Schubert3;

Celine Dudas4; Johanna Weth1; Almuth F. Keßler5

1Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,

Psychoonkologie, Würzburg, Deutschland

2Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik des

Universitätsklinikums, Funktionbereich Tumorlabor, Würzburg, Deutschland

3Universitätsklinikum Würzburg, Zentrum Innere Medizin, Zentrallabor -

Gerinnungsambulanz, Würzburg, Deutschland

4Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik des

Universitätsklinikums , Tumorbiologisches Labor , Würzburg, Deutschland

5Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik des

Universitätsklinikums, Neurochirurgie, Würzburg, Deutschland

Background: High-grade glioma patients and their caregivers oen suer

from psychological distress.1 Nevertheless, supportive services are lacking.

is study investigates whether a mindfulness-based yoga intervention is

feasible and aects anxiety, depression, quality of life, and stress-associ-

ated physiological parameters.

Methods: A monocentric on-site pilot study to test feasibility was started

in 2020 and then adapted to an online format due to the COVID-19 pan-

demic. Participants were randomly assigned to immediate intervention

and 8-weeks wait-list control groups. At randomization, immediately

before and aer the end of the 8-week intervention (1 h/week), which

was performed by trained yoga teachers in a synchronous format, as well

as another 3 months later, validated questionnaires were lled by partic-

ipants and serum plus saliva samples were taken. In addition, participants

were asked to rate their satisfaction with various course features.

Results: A total of 43 participants with 27 donating biological samples

and a drop-out of 14 were included. No signicant changes in subjective

criteria and physiological stress parameters were detected. Known disad-

vantages of online interventions were reported, e.g. technical diculties.

Overall course-satisfaction, with teachers guidance most positively rated,

was reported.

Discussion: High-grade glioma patients are very vulnerable due to their

rapidly changing health status. Caregivers oen have very limited time

due to the care they provide. erefore, recruitment is dicult and leads

to dropouts. Validity of the results may be limited due to the small sample

size and comparability of stress parameters due to circadian uctuations

in salivary cortisol.

Conclusion: e online yoga course is feasible. Despite of lacking per-

sonal contact, supervision of participants is possible and satisfactory. To

measure cortisol, more reliable hair samples will be taken in the upcoming

multicenter study, starting in fall 2021.

Indication of source: 1 Renovanz M et al. Front Neurol 2018

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts206

569

Qualitative interview study to assess care needs among

aected with Li-Fraumeni syndrome in Germany

Sarah Schott1; Juliane Nees1; Senta Kiermeier2; Imad Maatouk2

1Heidelberg, Universitätsfrauenklinik, Heidelberg, Deutschland

2Heidelberg, Klinik für Allgemeine Innere Medizin und Psychosomatik,

Heidelberg, Deutschland

Purpose: Li-Fraumeni syndrome (LFS) is a rare cancer predisposition

syndrome with a lifetime risk of up to 100% suering at least one malig-

nancy from birth onwards. Aected people claim distress and insucient

surveillance structures. Yet, little is known about LFS specic needs within

Germany.

Methods: A qualitative study was conducted to assess the needs of the

target group in order to develop an online intervention to support this

underserved group. Adults with a (likely) pathogenic TP53 variant could

participate with written consent. A study-specic semi-structured inter-

view guide was developed based on clinical experience and literature.

e guideline examined experiences and attitudes towards surveillance,

psychosocial stress and care, media, health system, participatory deci-

sion-making and issues regarding social environment (family; partner/

friends; career).

All interviews were conducted by one psychologist. Interviews were

transcribed verbatim. Qualitative content analysis of the transcribed

interviews was performed based on the principles of inductive and deduc-

tive category development.

Results: Between March - October 2020, 20 interviewees (f: 17; m: 3) aged

25 -67 (median 36) were enrolled. Most participants had suered cancer

themselves (85%) and had either children with childhood cancer (15%) or

parents and/or siblings with a diagnosis of LFS (68%).

irteen categories, summarized in four overarching topics were iden-

tied: e.g. fear of progression and distress, care supply, communication,

LFS in everyday life.

Discussion: People with LFS have overlapping issues in everyday life, pri-

vately and socially dealing and coping with their diagnosis. Comprehensive

care needs can be derived from the results, which are to be addressed in a

further step within the framework of an online intervention.

Conclusion: Specic communicative strategies and interdisciplinary sup-

ply structures are need in order to reduce the burden of LFS.

Funding: Federal Ministry of Education and Research ADDRESS Project

Grant Number: 01GM1909D

Disclosure Statement: e authors declare no conict of interest.

610

Web-based cognitive behavioral therapy for cancer-related

fatigue among survivors of Hodgkin lymphoma – a feasibility

study

Peter Esser1; Horst Müller2; Peter Borchmann2; Stefanie Kreissl2;

Uwe Platzbecker3; Vladan Vucinic3; Hans Knoop4;

Anja Mehnert-Theuerkauf1

1Abteilung für Medizinische Psychologie und Medizinische Soziologie,

Universitätsklinikum Leipzig, Leipzig, Deutschland

2Deutsche Hodgkin Studiengruppe, Klinik I für Innere Medizin,

Universitätsklinikum Köln, Köln, Deutschland

3Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie,

Universitätsklinikum Leipzig, Leipzig, Deutschland

4Abteilung für Medizinische Psychologie, Universitätsklinikum Amsterdam,

Amsterdam, Niederlande

Background: Hodgkin lymphoma is the most frequent malignancy in

young adults. Even though many patients can be cured, cancer-related

fatigue (CRF) is a frequent cause for long-term morbidity. We investi-

gated the feasibility of a web-based cognitive-behavioral therapy (CBT) to

reduce severe CRF among HL survivors.

Methods: We conducted a bi-centric before-and-aer study to adapt and

preliminary test the CBT among severely fatigued HL survivors. Patients

were primarily recruited via the German Hodgkin Study Group (GHSG)

and assessed at baseline (t0), post-treatment (t1) and 3-months follow-up

(t2). We primarily analysed feasibility including response and drop-out

rate. Secondary outcomes assessed preliminary ecacy including CRF

(CIS-Fat and EORTC-QLQ FA-12), quality of life (QoL; EORTC-QLQ

C30) and depressive symptomatology (PHQ-9). T-tests were used to com-

pare baseline with t1 and t2, respectively.

Results: Among 79 eligible patients contacted via the GHSG, 33 provided

initial interest (response rate: 42 %). Of the 17 participants, four patients

were treated face-to-face as pilot patients, 13 patients underwent the web-

based version. Ten patients completed the treatment (drop-out rate: 41

%). Intent-to-treat analyses revealed signicant improvements in both

CRF scores, depressive symptomatology and QoL (p ≤ .03). e eects in

CIS-Fat remained signicant at t2 (p = .03). Except for QoL, eects at t1

were replicated among the eight completers of the online version (p ≤ .04).

Discussion/conclusion: We found preliminary ecacy of the program

which warrants further research. Results on feasibility will help to design

a future RCT.

Disclosure Statement: e authors declare no conict of interest.

616

Depression; anxiety and distress screeners on the need and

utilization of psychosocial services among cancer survivors

Franziska Springer1; Leon Sautier2; Georgia Schilling3; Uwe Koch-Gromus2;

Carsten Bokemeyer3; Michael Friedrich1; Anja Mehnert-Theuerkauf1;

Peter Esser1

1University Medical Center Leipzig, Department of Medical Psychology and

Medical Sociology, Leipzig, Deutschland

2University Medical Center Hamburg-Eppendorf, Department of Medical

Psychology, Hamburg, Deutschland

3Department of Oncology, Hematology, and Bone Marrow Transplantation

with Section of Pneumology, University Medical Center Hamburg‐Eppendorf,

Hamburg, Deutschland

Background: Distress screening is recommended within routine clini-

cal cancer care to identify patients in need for psychosocial support. It is

however not clear whether distress screeners can be used for appropriate

psychosocial care planning and thus whether they can predict dierent

levels of readiness to use psychosocial support.

Methods: In a secondary analysis of a cluster intervention study, adult

cancer patients were assessed with three established distress screeners (DT,

PHQ-9, GAD-7) at baseline. e levels of readiness to use psychosocial

support, that is, need, intention and utilization, were binary assessed for

dierent psychosocial services aer 3 and 6 months. Logistic regression

models were applied to investigate the predictive eect of the screeners

on the levels of readiness. All models were corrected for multiple testing.

Result: 660 patients were included in the study, 46% were female and the

average age was 60 years. At the 3-month and 6-month follow-up, 353 and

259 patients participated, respectively. e PHQ-9 and GAD-7 predicted

the levels of readiness more oen than the DT did. Generally, the screen-

ers were best in predicting the need of the services, while the actual uti-

lization of the services was not predicted by any of the distress screeners.

Discussion and Conclusion: e three distress screeners might be useful

in psychosocial care planning, as they are all able to predict the need for

psychosocial support, and the PHQ-9 and GAD-7 further predict to some

degree the intention to use psychosocial support. Future research needs

to examine potential barriers and supporting factors that may explain the

utilization of psychosocial services.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 207

699

Psychosocial aftercare of adolescent and young adult cancer

survivors in Germany: Awareness, utilisation, satisfaction and

associated factors

Annekathrin Sender1; Michael Friedrich1; Katja Leuteritz1; Diana Richter1;

Florian Lordick2; Kristina Geue1

1University of Leipzig, Department of Mental Health, Medical Psychology and

Medical Sociology, Leipzig, Deutschland

2University of Leipzig, Medical Center, University Cancer Center, Leipzig,

Deutschland

Background: Young adult cancer patients have come into scientic focus

in recent years due to their high survival rate, among other things, but

also due to an increased psychological burden. Research ndings indicate

a lack of adequate care, and to date oer little insight into the current psy-

chosocial care situation. is study systematically assesses the awareness

of, utilisation of and satisfaction with psychosocial care for young adult

cancer survivors.

Methods: Survivors between 18 and 39 years were surveyed in aercare.

Awareness of, utilisation of and satisfaction with psychological coun-

selling (PC), social-legal counselling (SLC) and other psychosocial care

(OPC) were measured using self‐developed questionnaires. Multivariate

analyses were conducted to determine factors correlated with awareness

and use of psychosocial care.

Result: 514 survivors participated; the mean age at diagnosis was 29.6

years (SD=6.14). 54% of cancer survivors were aware of PC, 45% of SLC

and 24% of OPC. ose who possessed knowledge about these services

used it to a considerable extent (63%–74%), and the majority (66%–75%)

was highly satised. No common factors could be found that increase

the likelihood of being aware of these three services (R2 = 0.028–0.138).

Female gender (OR=2.08–2.18) and high anxiety (OR=1.19–1.38) were

identied as common factors that increase the likelihood of utilising psy-

chosocial services (R2 = 0.160–0.395).

Discussion: Survivors who are aware of psychosocial services in aercare

are motivated to use them and express high satisfaction with use. For the

utilisation of psychosocial services, anxiety and female gender can be

identied as common factors.

Conclusion: e visibility of psychosocial services for aercare should be

increased given the high number of unaware young adult survivors. e

active and repeated addressing of psychosocial issues and regular provi-

sion of information (e.g., written guides on survivorship) by caregivers

should be made a standard of care for this group.

Disclosure Statement: e authors declare the following: Förderung durch die

Deutsche Krebshilfe (Grant No.: 110948).

705

The components of the new form of care isPO: Result of the

innovation fund project on integrated, cross-sectoral

psycho-oncology

Hildegard Labouvie1; Vera Schiewer1; Natalie Talalaev1; Anne Klein1;

Peter Haas2; Michael Kusch1

1Klinik I für Innere Medizin, Universitätsklinik Köln, Klinische Psychoonkologie/

Versorgungsforschung, Köln, Deutschland

2Medizinische Informatik, Fachhochschule Dortmund, Dortmund, Deutschland

Background: e Innovation Fund at the G-BA funded the project

isPO/’’Integrated, cross-sectoral psychooncology’’ for 54 months between

2017 and 2022 with approx. 9 million EURO. e result of the project is

the „new form of care isPO“ (nFC-isPO). According to the Innovation

Fund, the nFC-isPO can be oered nationwide if successful.

Methods: e nFC-isPO, which consists of a total of 6 components, was

developed on the basis of the evaluation model according to Issel [1] and

implemented at four locations in NRW. In order to demonstrate whether

the form of care meets the requirements for transfer into the German

health care system, the components were designed in relation to the

“Framework for planning and delivery of psychosocial oncology services” of

the “American Psychosocial Oncology Society task force” [2].

Result: e nFC-isPO consists of six components (C1-C6) that are avail-

able in care telematic form in order to be implemented in the standard care

of the German health care system. e components (C) include C1) health

care concept, C2) health care pathways, C3) health care network con-

cept, C4) health care management, C5) the „Computer-based Assistance

System: Psycho-Oncology“ and C6) IT-supported quality management.

Discussion: e six components of the nFC-isPO and their relation to the

framework of the APOS task force are presented.

Conclusion: e innovative nFC-isPO is designed according to interna-

tional standards of the APOS task force.

References:

1 Issel, LM (2014). Health program planning and evaluation: A practi-

cal, systematic approach for community health. Burlington, MA: Jones

& Bartlett Learning

2 Pirl WF, Greer JA, Gregorio SW-D et al. (2020). Framework for plan-

ning the delivery of psychosocial oncology services: An American

psychosocial oncology society task force report. Psycho-Oncology.

2020;29:1982-1987

Disclosure Statement: e authors declare no conict of interest.

717

Evaluation of the new form of care isPO using the framework

for planning the delivery of psychosocial oncology services

of the American Psychosocial Oncology Society (APOS) task

force

Michael Kusch1; Hildegard Labouvie1; Vera Schiewer1; Clarissa Lemmen2;

Peter Haas3

1Klinik I für Innere Medizin, Universitätsklinikum Köln, Klinische

Psychoonkologie/Versorgungsforschung, Köln, Deutschland

2Institut für Gesundheitsökonomie u. Klinische Epidemiologie der Universität zu

Köln, Universitätsklinikum Köln, Köln, Deutschland

3Medizinische Informatik, Fachhochschule Dortmund, Dortmund, Deutschland

Background: In 2020, the American Psychosocial Oncology Society

(APOS [1]) task force formulated the framework for planning the delivery

of psychosocial oncology services that could aid in planning services and

justifying requests for resources. e project isPO/integrated, cross-sec-

toral psycho-oncology, funded by the Innovation Fund of the G-BA,

aimed to develop a new form of care (nFC-isPO) that has the prospect

of being oered nationwide. e quality features of the nFC-isPO were

evaluated by an independent institute in 2018-21. e presentation will

answer the question of whether the quality features of the nFC-isPO also

meet the requirements of the APOS task force.

Methods: e nFC-isPO was developed according to Issel’s evaluation

theory [2] and implemented at four sites in NRW within a contract for

„special care“ according to § 140a SGB V. Quarterly quality circles (QC)

and quality workshops (QW) for quality improvement were conducted.

e quality improvement process of the nVF-isPO took place within the

framework of PDC/SA (plan, do check/study act) cycles and evaluation

reports by an independent evaluation institute.

Results: In a period of 27 months, 11 site-intern QC’s and 11 cross-site

QW’s were carried out, which were followed by a total of 18 PDC/SA

cycles for continuous quality improvement. e independent evaluation

institute submitted one prospective, two formative and one summative

report on the quality of care of the nVF-isPO. All results have to be evalu-

ated against the framework of the APOS task force.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts208

Discussion: In the presentation, the conformity of the nFC-isPO with the

APOS criteria will be presented and critically evaluated.

Conclusions: e quality of care of nFC-isPO meets the criteria of the

APOS task force.

References:

1 Pirl WF et al. (2020). Framework for planning the delivery of psycho-

social oncology services: An American psychosocial oncology society

task force report. Psycho-Oncology. 2020;29:1982-1987.

2 Issel, LM (2014). Health program planning and evaluation: A practi-

cal, systematic approach for community health. Burlington: Jones &

Bartlett Learning.

Disclosure Statement: e authors declare no conict of interest.

722

Causal attributions, controllability and changes in health

behavior among women carrying a BRCA1/2-mutation

Katharina Klein1; Dorothee Speiser2; Hannah Brand1; Friederike Kendel1

1Charité – Universitätsmedizin Berlin, Institute of Gender in Medicine, Berlin,

Deutschland

2Charité – Universitätsmedizin Berlin, Department of Gynecology with Breast

Cancer, Berlin, Deutschland

Background: Health behavior is becoming increasingly important for

women carrying a BRCA1/2-mutation regarding the ability to inuence a

disease. Furthermore, it is necessary to clarify whether women are aware

of the causes of cancer, as their assumptions do not always align with the

medical evidence. e aim of the study was to investigate which causal

attributions BRCA1/2-mutation carriers make and if they assume that

they can inuence the development of (renewed) cancer through preven-

tion measures and their health behavior. Additionally, it should be inves-

tigated whether BRCA1/2-mutation carriers have changed their health

behavior.

Methods: As part of a cross-sectional questionnaire study, women carry-

ing a BRCA1/2-mutation (N=100) were asked about causal attributions,

controllability and changes in health behavior. In the statistical analysis,

descriptive statistical methods, t- and chi-square tests as well as correla-

tion analyzes were applied and calculated.

Result: In addition to heredity (97.0%), the women also named stress

(82.0%), health behavior (82.0%), environmental factors (80.0%) and

personality (62.0%) as causes for cancer. Most of the study participants

believed that they could inuence their own disease risk to a large extent.

With regards to individual health behaviors, the women ate healthier

(p<.001), were more physically active (p=.004) and tried to keep their

stress level low (p=.003). Causal attribution and controllability were asso-

ciated with changes in health behavior.

Discussion: e results demonstrate the importance of incorporating

behavior information into health care as well as specically asking women

what they perceive to be the causes of cancer.

Conclusion: e study underlines the importance of subjective param-

eters for the adaptation to a life with a BRCA1/2-mutation and shows

a great need for research in this regard, e.g. with regard to digital sup-

port oers in care from a medical, psychological and also health science

perspective.

Disclosure Statement: e authors declare that they have no conict of interest.

731

A comparative analysis of the long-term eects of cancer

therapy on survivors enrolled in the University Cancer Center

Hamburg (UCCH) Clinical Survivorship Registry: a cohort

study

Carrie-Ann Minto1; Barbara Koch1; Ann-Kathrin Ozga2;

Antonia Beitzen-Heineke1; Sarah Dwinger3; Marianne Sinn1;

Carsten Bokemeyer1; Alexander Stein1; Julia Mann1; Jannike Salchow1

1Universitätsklinikum Hamburg Eppendorf, II. Medizinischen Klinik und

Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung

für Pneumologie), Hamburg, Deutschland

2Universitätsklinikum Hamburg Eppendorf, Zentrum für Experimentelle

Medizin, Institut für Medizinische Biometrie und Epidemiologie, Hamburg,

Deutschland

3Universitätsklinikum Hamburg Eppendorf, Zentrum für Psychosoziale Medizin,

Institut und Poliklinik für Medizinische Psychologie, Hamburg, Deutschland

Background: As cancer rates increase and mortality decreases, the num-

ber of survivors will rise. Cancer therapy causes lasting side-eects that

impact well-being. is study aims to report prevalences of distress,

depression, anxiety, fatigue and level of unmet needs; and assess the inu-

ence of age, sex, primary diagnosis, treatment modality (TM) and time

since diagnosis (TSD).

Methods: Subjects were recruited from the UCCH survivorship program

and at rst appointment completed 5 questionnaires (DT, SCNS-SF34,

PHQ-9, GAD-7 & FACIT-F). Demographics and prevalences were

reported for the group and selected cohorts (age: 18-39, 40-64, 65+; sex;

primary diagnosis: lymphoma, leukemia, gastrointestinal, gynecological,

sarcoma, other; TM: multimodal, local, systemic; TSD: 0-2, 3-5, 6-10, 10+

years). Multivariable linear/logistic regression and pairwise comparison

were run on cohorts to assess the odds of reporting clinically relevant out-

come levels.

Results: From Jan. 2015 to Mar. 2020 449 survivors were screened - 435

included. Overall, 57.2% reported clinically relevant distress levels. For

depression: mild (30.1%), moderate (15.4%), moderately-severe (5.3%)

and severe (1.8%) symptoms were reported. 78% reported the likely pres-

ence of an anxiety disorder. 29.2% reported clinically signicant fatigue.

Mean summated Likert scores ±SD for unmet needs: psychological

19.97±10.497, health systems & information 23.62±13.939, physical &

daily living 9.19±4.607, patient care & support 8.30±4.592 and sexuality

5.01±3.062. e impact analysis indicated that age and primary diagnosis

had the greatest inuence, followed by sex, TSD and TM.

Discussion: In most outcomes over half of respondents reported clini-

cally relevant levels, showing how strongly the long-term eects of ther-

apy aect survivors. Whilst the impact analysis provides key insights into

what did, and perhaps more interestingly, did not strongly inuence the

outcomes.

Conclusions: Based on the ndings, future research could seek to better

understand the inuence of age, sex, diagnosis, TM and TSD.

Disclosure Statement: e authors declare no conict of interest.

743

Transferabillity of the new form of care isPO into the German

health care system

Michael Kusch; Vera Schiewer; Hildegard Labouvie

Klinik I für Innere Medizin, Universitätsklinikum Köln, Klinische

Psychoonkologie/Versorgungsforschung, Köln, Deutschland

Background: e Innovation Fund (IF) has funded the project isPO/

integrated, cross-sectoral psycho-oncology. e project was intended to

implement the goal of the National Cancer Plan to further develop „onco-

logical care structures and quality assurance“. In the isPO project, a new

form of care (nFC-isPO) was developed and implemented. According to

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 209

the IF, the nFC-isPO project could be oered nationwide if successful. e

structure and process quality of the nFC-isPO was evaluated by an inde-

pendent Institute of Medical Sociology, Health Services Research, and

Rehabilitation Science (IMVR) in the period 2018-2021. In addition, the

management of the isPO consortium has checked whether the nFC-isPO

meets the requirements of the American Psychosocial Oncology Society

(APOS) task force for high quality psychosocial oncology services [1].

Methods: During the one-year development phase of isPO (2018), the

IMVR used methods of prospective evaluation to test the implementabil-

ity of the nFC-isPO. In the two-year implementation phase (2019-2020),

nFC-isPO was provided under selective contract conditions (§ 140a SGB

V). e IMVR used formative evaluation methods to examine the condi-

tions under which nVF-isPO could be transferred to standard care. e

APOS task force requirements for high quality psychosocial oncology ser-

vices were reviewed taking into account the ndings from the evaluation

of the nFC-isPO.

Results: e nal summative evaluation report of the IMVR will be

completed in April 2022. Even though the report is not yet available, it is

already possible to demonstrate the transferability of the nFC-isPO into

the German health care system.

Discussion: e transferability of the nFC-isPO to selective-con-

tract-based care in the German health system will be presented.

Conclusions: e nFC-isPO can serve as a model for the transfer of psy-

cho-oncology into the German health care system.

Reference:

1 Pirl WF et al. (2020). Framework for planning the delivery of psycho-

social oncology services: An American psychosocial oncology society

task force report. Psycho-Oncology,29:1982-1987.

Disclosure Statement: e authors declare no conict of interest.

762

Evaluation of the access process to psycho-oncology

care:results from the German integrated, cross-sectoral

psycho-oncology programme (isPO)

Anne Klein; Vera Schiewer; Hildegard Labouvie; Michael Kusch

Klinik I für Innere Medizin, Universitätsklinik Köln, Klinische Psychoonkologie/

Versorgungsforschung, Köln, Deutschland

Background: e Innovation Fund at the G-BA funds the project isPO

(integrated, cross-sectoral psycho-oncology). e project is intended to

implement the demand of the Federal Government’s National Cancer

Plan to further develop “oncological care structures and quality assur-

ance” [1]. Although many cancer patients experience high levels of emo-

tional distress, only a small proportion make use of psycho-oncological

care (POC). One reason is that the process of referral to POC has not been

uniformly structured in oncology centers so far. Within the framework of

the isPO program, care pathways for the access process (AP) have been

formulated to ensure the accessibility and timeliness of POC according to

the quality indicators of the ÄZQ [2].

Methods: To ensure a timely access to POC, referral bills have been devel-

oped. Using the referral bills, the attending physician informs a patient

about POC, records the patient’s subjective need to participate and initi-

ates POC. Specic dates in the AP such as admission date, date of med-

ical information, referral and patient enrolment were documented. e

quality criteria accessibility and timeliness and program adherence were

investigated using a mixed methods design.

Result: Preliminary results show that 2.257 patients were assigned to

the nfc-isPO within 12 months. e rates of accessibility vary per clinic

between 0% and 31,4%. of the initial access process showed an average

process duration of 42 days (SD = 43.8).

Discussion: Comparison of the quantitative and qualitative results shows

that deviations from the AP have a negative inuence on accessibility and

timeliness.

Conclusions: Regular information to all care providers about the POC

oered and the AP is essential.

Source:

1 Bundesministerium für Gesundheit. Ziele des Nationalen Krebsplans. 2017.

2 Ärztliches Zentrum für Qualität in der Medizin. Qualitätskriterien und Quali-

tätsindikatoren. 2020

Disclosure Statement: e authors declare no conict of interest.

804

Psychological distress in German sarcoma patients—Results

of an large, observational, multicenter Study (PROSa)

Martin Eichler; MSc.1,2; Leopold Hentschel1; Beate Hornemann1;

Stephan Richter2; Susanne Singer3; Peter Hohenberger4; Bernd Kasper5;

Dimosthenis Andreou6,7; Daniel Pink6,8; Karin Arndt9; Martin Bornhäuser1,2;

Jochen Schmitt1,10; Markus K. Schuler2

1National Center for Tumor Diseases (NCT/UCC), University Hospital Dresden

2Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav

Carus

3Institute for Medical Biostatistics, Epidemiology and Informatic, University

Hospital Mainz

4Division of Surgical Oncology & Thoracic Surgery, Mannheim University

Medical Center, University of Heidelberg

5Sarcoma Unit, Mannheim Cancer Center, Mannheim University Medical Center,

University of Heidelberg

6Sarcoma Center Berlin-Brandenburg, Helios Hospital Bad Saarow

7Department of General Orthopedics and Tumor Orthopedics, University

Hospital Münster

8Department of Internal Medicine C, University Hospital Greifswald

9German Sarcoma Foundation

10Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus

Background: Sarcomas are a group of rare, heterogeneous tumors of

mesenchymal origin. Psychological distress diers widely between cancer

types and has rarely been analyzed in sarcoma patients. We aimed to iden-

tify the prevalence of distress in this group and to investigate associated

factors.

Methods: e PROSa (Burden and medical care of sarcoma in Germany)

cohort study was conducted between 2017 and 2020 in 39 German study

centers. For the present analysis, cross-sectional data of adult patients

with sarcoma of any entity were analyzed. Distress was measured with the

Patient Health Questionnaire (PHQ‐4). Associated factors were analyzed

exploratively using multivariable logistic regression models. We included

socio-economical, medical, and patient reported variables with stepwise

backward variable selection.

Result: We included 1095 patients. Prevalence of anxiety was 17.1%,

of depressiveness 19.9%. 26.9% had one or both. In the nal model liv-

ing with children (no vs yes Odds Ratio (OR): 1.6), employment status

(employed vs unemployed OR: 3.3; employed vs disability pension OR:

1.7), fatigue, decreased physical functioning, pain, and time since diag-

nosis (<12month vs. all other) were signicantly associated with distress.

Discussion/ Conclusion: Prevalence of distress is high in sarcoma

patients. With this large observational study, we were able to identify

vulnerable groups for anxiety and depressiveness. Prevalence seems

highest within the rst year aer diagnosis, in patients with low physi-

cal functioning, high fatigue and high pain and in those living in certain

socio-economic conditions (living with children, unemployment, disabil-

ity pension). Clinicians and psycho-oncologist should be aware of these

factors and sensitized for the social aspects of psychological distress.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts210

857

Use of psycho-oncological care after cancer diagnosis –

analysis of inuencing factors

Hannah Reuter1; Jochen Ernst2; Ute Goerling3; Beate Hornemann4;

Anja Mehnert-Theuerkauf2; Tanja Zimmermann1

1Medizinische Hochschule Hannover, Klinik für Psychosomatik und

Psychotherapie, Hannover, Deutschland

2Universitätsklinikum Leipzig, Abteilung für Medizinische Psychologie und

Medizinische Soziologie, Leipzig, Deutschland

3Charité- Universitätsmedizin Berlin, Charité Comprehensive Cancer Center

(CCCC), Berlin, Deutschland

4Uniklinikum Dresden, Nationales Centrum für Tumorerkrankungen, Dresden,

Deutschland

Background: e 2008 National Cancer Plan calls the expansion of psy-

cho-oncological care structures. Given the limited nancial and human

resources and the increasing number of cancer patients, planning of

psycho-oncological care according to the needs becomes increasingly

important. erefore, it is necessary to examine the current status of psy-

cho-oncological care with regard to 1. the use of psycho-oncological care

and 2. the identication of factors inuencing the use, need and demand

of psycho-oncological care. e aim of the study is to identify moderat-

ing factors such as mental distress, socioeconomic status and sociodemo-

graphic aspects, in addition to analyzing actual use, in order to ensure that

psycho-oncological care support is planned in a tailored manner.

Methods: In the longitudinal multicenter study (Leipzig, Berlin, Hanover,

Göttingen, Dresden) ‘LUPE’ (longitudinal analysis of the psycho-onco-

logical demand of patients and their relatives, stratied to biopsychoso-

cial inuencing factors), 1000 patients are surveyed at four measurement

points from diagnosis to follow-up at 6-month intervals. e survey con-

sists of standardized questionnaires and a diagnostic interview (Structured

Clinical Interview for DSM-5). For the present survey, the questionnaire

on mental distress, support needs, and use of psycho-oncological care are

analyzed at the time of the initial measurement.

Result: Initial results are expected by June 2022 and will be presented at

Congress.

Discussion: Signicant dierences in utilization are expected to be found

based on cancer type as well as socioeconomic status and sociodemo-

graphics. Further discussion will be possible with the rst results.

Conclusion: e results of inuencing factors of utilization, need, and

demand should improve the psycho-oncological support structure

Disclosure Statement: e authors declare no conict of interest.

888

Challenges in shared decision-making when prognosis is

limited: development and testing of a decision aid for patients

with advanced lung cancer

Matthias Villalobos-Bollen; Laura Unsöld; Nicole Deis; Anja Siegle;

Michael Thomas

Universitätsklinikum Heidelberg, Thoraxklinik, Internistische Onkologie,

Heidelberg, Deutschland

Introduction: Shared decision-making (SDM) is of increasing impor-

tance in oncology. Decision aids (DA) can help patients to be more

actively involved in the process. ere is still a decit in implementation

in every-day practice and a lack of instruments for specic settings like

advanced cancer with limited prognosis. Patients and health care pro-

viders are challenged by balancing constantly evolving therapeutic algo-

rithms (new treatment options that oen only show marginal benets)

with end-of-life decision-making. erefore, the aim of our study is to

explore and develop specic tools to facilitate the decision-making pro-

cess in metastatic lung cancer.

Methods: Study components include: (1) literature review, (2) semi-struc-

tured guideline-interviews with 9 patients, 6 relatives and 5 health care

professionals (qualitative content analysis following Kuckartz), (3) devel-

opment of DA, (4) feedback from patient support group members (think-

aloud method) and experts, (5) revision and pilot testing.

Results: Review of existing DA for advanced lung cancer showed the lack

of theoretical foundation and reection on personal values. Interviews

revealed that the process of decision-making was mainly characterized by

a lack of perceived options and the missed presentation of “best support-

ive care” (BSC) as an alternative. Our DA was developed using the “con-

ict model of decision-making” (Janis & Mann) and the “four models of

the physician-patient relationship” (Emanuel & Emanuel). Aer feedback

and revision, it includes the topics: information preferences, preferences

in participation, reection on personal values and option-grid including

palliative care. Pilot testing showed acceptance and feasibility.

Conclusions: Being confronted with limited options that only include

active cancer treatment, patients choose a more paternalistic decision

model hazarding the timely integration of palliative care and transition to

BSC. Developing a DA should empower patients to address their personal

values and their preferred role in SDM to achieve goal-concordant care.

Disclosure Statement: e authors declare no conict of interest.

889

Online versus face-to-face – how do video consultations

associate with the doctor-patient-interaction?

Friederike Kendel1; Caren Hilger1; Selamawit Woldai2; Markus Feufel2

1Gender in Medicine, Charité - Universitätsmedizin Berlin, Berlin, Deutschland

2Institut für Arbeitswissenschaft, Technische Universität Berlin, Berlin,

Deutschland

Purpose: Since the corona pandemic, the use of video consultation has

increased markedly. For vulnerable groups such as oncological patients,

the advantages seem obvious. But how, compared to face-to-face con-

sultation, does video consultation potentially change the doctor-patient

relationship? Which barriers may hinder the eective use of this con-

sultation format in practice? We are presenting rst results from a study,

funded by Federal Ministry of Health, which will provide the basis for a

hands-on guide for both physicians and patients on how to improve the

video consultations.

Methods: We use a quasi-experimental mixed-methods design to analyze

qualitative and quantitative dierences between face-to-face and video

consultations. Data collection will be completed by June 2022. We will

record N = 64 videos (n = 32 for each consultation format) with gyneco-

logical and urological cancer patients. Aer the consultation, all patients

answer a questionnaire with questions about their consultation experi-

ence. For quantitative analyses, the counseling sessions will be systemati-

cally compared in terms of verbal and nonverbal communication patterns.

Relative frequencies of eye contact and the information exchanged will be

compared using χ2 -tests. e validated questionnaire MAPPIN’Obsdyad

will be used to assess the quality of shared decision-making parameters. In

addition, semi-structured interviews will be conducted with n = 10 physi-

cians and n = 10 patients experienced with video consultation, for which

a qualitative content analysis will be conducted.

Expected results: We present a complex methodological approach we

used to approach the comparison of video vs. face-to-face consultations.

We will also present rst evidence on how video consultations change the

doctor-patient interaction.

Discussion: We show possible limitations and barriers of video consulta-

tions. Within the framework of a Delphi process, we will use the results to

develop recommendations outlining best practices of video consultations

for both physicians and patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 211

961

Navigating the German Health Care System for Financial

Support – Breeding ground for Subjective Distress. A

Qualitative Interview-Study with Cancer Patients in Germany

Andrea Züger1; Viktoria Mathies2; Katja Mehlis1; Sophie Pauge3;

Bastian Surmann3; Luise Richter4; Thomas Ernst2; Wolfgang Greiner3;

Natalja Menold4; Eva Caroline Winkler1

1National Center for Tumor Diseases (NCT), Section of Translational Medical

Ethics, Ethics and Patient oriented Care in Oncology, Heidelberg, Deutschland

2Jena University Hospital, Department of Internal Medicine, Hematology and

Internal Oncology, Jena, Deutschland

3Bielefeld University, School of Public Health, Health Economics and Health Care

Management, Bielefeld, Deutschland

4Dresden University, Institute of Sociology, Methods in Empirical Social

Research, Dresden, Deutschland

Background: A tumor disease can cause high treatment costs and loss

of income. In Germany, a universal healthcare and social welfare system

with dierent providers covers parts of these direct and indirect costs.

However, to obtain payments, patients need to cooperate with health

insurers and social security providers. ese interactions can be frustrat-

ing and exhausting. ere is evidence that bureaucratic burdens nega-

tively aect health outcomes[1]. As a part of a study on nancial eects of

a tumor disease, we investigated patient-reported subjective distress due

to the administrative hurdles they face within the health care system.

Methods: Semi-structured interviews with 18 cancer patients were con-

ducted. Patients were recruited in outpatient (National Tumor Center

Heidelberg) and inpatient (University Hospital Jena) settings. e inter-

views were transcribed verbatim. Qualitative content analysis was used to

identify categories causing subjective distress.

Result: Four categories were identied: extensive eort (1), communica-

tion with providers (2), insucient knowledge and problem of compre-

hension (3), and compulsion to make decisions (4).

Discussion: Financial eects of tumor diseases consist of objective nan-

cial burden (direct and indirect costs) and subjective nancial distress.

Administrative and bureaucratic obligations of patients within the health

care system are strongly associated with both. Obstacles and administra-

tive conicts can limit options of action and result in loss of control, which

in turn results in subjective distress and distrust in the health care system.

Conclusion: Financial eects of tumor diseases in a universal healthcare

setting are multidimensional. In order to better understand and mea-

sure them and develop a patient-reported tool, the bureaucratic burdens

should not be ignored.

Reference:

[1] Herd, P & Moynihan, D. How Administrative Burdens Can Harm

Health, Health Aairs Health Policy Brief; 2020. doi/10.1377/

hpb20200904.405159/full/.

Disclosure Statement: is research is funded by Deutsche Krebshilfe.

996

Together against suicidal ideation and behavior in cancer

patients: The TASC study

Mareike Ernst1; Rüdiger Zwerenz1; Jörg Wiltink1; Elmar Brähler1;

Tamara Schwinn1; Judith Hirschmiller1; Konstantin Strauch2;

Nestor Kapusta3; Manfred E. Beutel1

1Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,

Deutschland

2Institut für Medizinische Biometrie, Epidemiologie und Informatik,

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,

Deutschland

3Universitätsklinik für Psychoanalyse und Psychotherapie, Medizinische

Universität Wien, Wien, Österreich

Background: Cancer can implicate great psychological distress, including

dangerous suicidal ideation and behavior. However, prevalence rates and

risk/protective factors of suicide outcomes in cancer patients and survivors

have hardly been studied in German-speaking countries. Furthermore, it

is currently unclear whether potentially vulnerable patients are adequately

screened by health care providers.

Methods: e project combines analyses of existing data (including a

prospective community cohort and psychotherapeutic intervention stud-

ies) and a new data collection of patients treated at the University Cancer

Center Mainz (UCT Mainz). In total, data from over 24,500 individuals,

among them more than 2,400 cancer patients/survivors, will be used. e

question of whether suicidal ideation in cancer patients is adequately

explored will be investigated using both qualitative (a detailed analysis

of care at the UCT Mainz through interviews with dierent professional

groups) and quantitative methods (a nationwide expert survey).

Result, Discussion, and Conclusion: e project will give insight into

prevalence rates of suicide outcomes in individuals aected by cancer

(according to diagnosis group, time since diagnosis, and compared to

representative population samples). It will also yield in-depth knowledge

of characteristics, psychological and social variables, and behaviors shap-

ing the risk of suicidal crises in the context of cancer, with a focus on

modiable factors that can be addressed by intervention and prevention.

Lastly, it will shed light on potential barriers standing in the way of the

recommended care. Integrating these ndings, the overarching goal is to

contribute to strengthening evidence-based suicide prevention eorts in

cancer patients and survivors.

Disclosure Statement: e authors declare no conict of interest.

1018

Advice and support for lung cancer patients and their

relatives: A randomized controlled trial

Julia Dusel1; Hanna Arnold1; Antonia Rabe2; Horst-Dieter Hummel3;

Pius Jung4

1Julius-Maximilians-Universität Würzburg , Medizinische Fakultät, Würzburg,

Deutschland

2Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,

Psychoonkologie , Würzburg, Deutschland

3Universitätsklinikum Würzburg, Interdisziplinäres Studienzentrum mit ECTU

CCC Mainfranken, Würzburg, Deutschland

4Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik I -

Pneumologie, Würzburg, Deutschland

Background: e high incidence combined with the high lethality and

bad prognosis highlight the need for psycho-oncological care for patients

as well as their relatives. e primary aim of the study is to investigate the

eects of a more structured care for relatives based on the evidence-based

CALM-Manual (Managing Cancer And Living Meaningfully). In addi-

tion, we investigate to what extent the support of relatives also has an indi-

rect positive eect on patients’ well-being.

Methods: Adult participants regardless of stage of disease or treatment

will be randomly assigned to control-group (CG) or to intervention-group

(IG). Patients as well as their relatives complete assessments at baseline.

Subsequently relatives in the IG receive structured care (3-6 sessions

with psycho-oncologists) and the CG receives standard psycho-oncolog-

ical care. No specic intervention is oered to patients in boths study-

arms, but they can request psycho-oncological support as usual. Patients

as well as relatives receive second assessments post-intervention (IG) or

aer 6 weeks (CG). Assessments examine depression (PHQ-9), anxiety

(GAD-7) and distress (Distress thermometer). Additionally relatives

receive questions about supportive needs (SCNS-SF34-G) and quality of

life (CQOLC). Primary endpoint is a signicant change in GAD-7 of the

IG compared to the CG. Its statistical evaluation is done by a t-test. Power

calculations reveal the need to enroll 88 subjects.

Result: Recruitment is still ongoing. Due to the higher intensity of the

CALM-Intervention, it is expected that the relatives in IG will show greater

improvements in psychological distress and quality of life compared to

those in CG. In addition, the support of the relatives is also presumed to

have an indirect positive impact on patient well-being, depending on its

intensity.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts212

Discussion: If an eect can be demonstrated, this can help improve care

for the target group.

Disclosure Statement: e authors declare no conict of interest.

1030

App-based psycho-oncological support for cancer patients to

improve distress – a randomized controlled trial

Franziska Springer1; Ayline Maier2; Michael Friedrich1; Jan Simon Raue2;

Gandolf Finke2; Anja Mehnert-Theuerkauf1

1University Medical Center Leipzig, Medizinische Psychologie und Medizinische

Soziologie, Leipzig, Deutschland

2Fosanis Gmbh, Berlin, Deutschland

Background: Cancer patients oen suer from high levels of distress, but

access to psycho-oncological support is scarce, especially in rural areas.

erefore, digital psycho-oncological support, such as the app “Mika” by

Fosanis GmbH, oers immediate and permanently accessible support

for cancer patients. e aim of the study was to investigate the ecacy of

Mika on general distress.

Methods: Cancer patients of all types of tumors (³18 years) were recruited

online via Social Media ads and at the Leipzig medical center. In an RCT,

the intervention group (IG, N=99) received immediate access to the app,

whereas the wait list control group (CG, N=119) received access aer

12-weeks. Primary outcome was general distress, measures with the

NCCN distress thermometer. All outcomes were assessed online at base-

line, 2, 6 and 12 weeks. We applied intention-to-treat (ITT) and per-pro-

tocol analysis (PP), i.e., completion of all questionnaires, no app use in the

CG, compliant app use in the IG. Analysis of covariance was used to assess

the change from baseline to 12-weeks between groups.

Result: e mean age of the patients was 56 years, 61% were female. e

most frequent cancer types were breast cancer (34%) and hematological

cancer (28%). e drop-out rate was 16%. e analysis included 218 and

166 patients for ITT and PP, respectively. Both analyses revealed a sig-

nicant improvement of general distress in the IG, compared to the CG.

Eect sizes were small and classied as clinically relevant by a minimal

important dierence analysis.

Discussion and Conclusion: Mika is an eective app-based support

program for cancer patients to reduce general distress with eect sizes

comparable to other psycho-oncological interventions, such as psycho-

education or psychotherapy. However, there is scare literature on compa-

rable digital psycho-oncological support programs. Mika is a promising

opportunity to provide additional support to cancer patients during their

disease and therapy.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1057

Preliminary results on the feasibility and eectiveness of the

emotion-based psycho-oncological online self-help epos

Angeliki Tsiouris1; Anna Mayer1; Jörg Wiltink1; Christian Ruckes2;

Manfred E. Beutel1; Rüdiger Zwerenz1

1Universitätsmedizin Mainz, Klinik und Poliklinik für Psychosomatische Medizin

und Psychotherapie, Mainz, Deutschland

2Interdisziplinäres Zentrum Klinische Studien (IZKS) Mainz, Mainz, Deutschland

Background: Internet-based interventions are considered as a promising

oer for cancer patients to improve their psychological well-being and

overcome existing barriers to seeking psycho-social support. While exist-

ing psycho-oncological online interventions have primarily used behav-

ioral and mindfulness-based approaches, psychodynamic approaches

are underrepresented. With the online self-help program epos, the rst

German-language psycho-oncological online self-help program based on

psychodynamic concepts has been developed. e aim of the study is to

evaluate the feasibility and eectiveness of epos in reducing psychological

distress in people with cancer.

Methods: N=327 people with cancer participated in the randomized

controlled trial. Participants in the intervention group had access to the

online self-help program epos for 10 weeks, while participants in the

control group received treatment as usual and access to an informational

website. Participants completed questionnaires at three time points (T0

baseline, T1 post-intervention, T2 follow-up). An analysis of covariance

will be used to test the hypothesis of whether participants in the interven-

tion group report lower scores in psychological distress, measured by the

PHQ-ADS, at the end of the intervention period compared to participants

in the control group. Secondary outcomes include anxiety and depressive

symptoms, quality of life, emotion control, and posttraumatic growth.

Result: By the time of the congress, data collection and analyses will be

completed, allowing the presentation of preliminary results on the feasi-

bility and eectiveness of epos.

Discussion: e study results will be discussed with regard to limitations

and strengths of the study design.

Conclusion: As the rst German-language psycho-oncological online

self-help with a psychodynamic focus, epos might complement conven-

tional psycho-oncological treatment oers and contribute to the diversity

of psychotherapeutic orientations in the digital context.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 213

Quality-of-Life

Best-of-Abstract-Vortrag

358

Change towards a healthier lifestyle is associated with better

health-related quality of lifein long-term colorectal cancer

survivors

Ruth Elisa Eyl1,2; Melissa Thong3; Prudence Carr1; Lina Jansen1;

Jenny Chang-Claude4,5; Michael Homeister1; Hermann Brenner1,6,7;

Volker Arndt3

1Deutsches Krebsforschungszentrum, Abteilung Klinische Epidemiologie und

Alternsforschung, Heidelberg, Deutschland

2Klinikum Stuttgart, Stuttgart Cancer Center – Tumorzentrum Eva Mayr-Stihl,

Stuttgart, Deutschland

3Deutsches Krebsforschungszentrum, Cancer Survivorship, Heidelberg,

Deutschland

4Deutsches Krebsforschungszentrum, Genetic Epidemiology, Heidelberg,

Deutschland

5University Medical Center Hamburg-Eppendorf, University Cancer Center

Hamburg (UCCH), Cancer Epidemiology Group, Hamburg, Deutschland

6Deutsches Krebsforschungszentrum, Division of Preventive Oncology,

Heidelberg, Deutschland

7Deutsches Krebsforschungszentrum, German Cancer Consortium, Heidelberg,

Deutschland

Background: Lifestyle factors are important in tertiary prevention for col-

orectal cancer (CRC) survivors. To date, a few cross-sectional studies have

studied a combination of lifestyle factors and health-related quality of life

(HRQOL). Further, no study has investigated whether a change towards

a healthier lifestyle is positively associated with HRQOL in CRC survi-

vors years aer diagnosis. erefore, our study aimed to assess whether a

change in a combination of lifestyle factors was associated with HRQOL

up to 10 years post-diagnosis.

Methods: We used data from the prospective population-based DACHS

study for 2283 CRC survivors. A healthy lifestyle score (HLS) previously

developed by our research group was adopted. e HLS, derived from

ve modiable lifestyle factors (smoking, alcohol consumption, diet, body

fatness, and physical activity), were assessed at diagnosis, 5-year (5YFU),

and 10-year follow-up (10YFU). HRQOL was assessed by the EORTC

Quality of Life Questionnaire-Core 30 at 5YFU and 10YFU. Multivariable

linear regression and linear mixed models were used to explore associa-

tions between changes in the survivors´ lifestyle and HRQOL over time.

Results: Survivors who improved their HLS from baseline to 5YFU

reported better functioning, higher global health/QOL and less com-

plaints of fatigue and dyspnea at 5YFU than survivors who maintained

a high HLS from baseline to 5YFU. In longitudinal analyses, survivors

with an improved HLS reported better functioning during follow-ups,

although physical functioning decreased over time regardless of HLS.

Survivors with improved HLS reported generally less complaints with

fatigue, pain and dyspnea during follow-ups, in comparison to the groups

who maintained a low or decreased HLS.

Discussion: A change towards a healthier lifestyle was associated with

better functioning and less symptom burden.

Conclusion: Our results reinforce the importance of tertiary prevention

through the support of maintaining or promoting a healthier lifestyle

among long-term CRC survivors.

Disclosure Statement: e authors declare no conict of interest.

946

Longitudinal course of global health-related quality of life

and fatigue up to 5 years after radiotherapy in an

international multicentre observational cohort of men with

prostate cancer

Petra Seibold1; Miguel E Aguado Barrera2; David Azria3; Erik Briers4;

Renée Bultjinck5; Alessandro Cicchetti6; Ananya Choudhury7;

Sara Gutiérrez-Enríquez8; Thomas Heger1; Irmgard Helmbold1;

Rudolf Kaaks1; Maarten Lambrecht9; Tim Rattay10; Barry S Rosenstein11;

Dirk De Ruysscher12; Elena Sperk13; Hilary Stobart14; R Paul Symonds10;

Christopher J Talbot10; Riccardo Valdagni6,15; Ana Vega2; LIV Veldeman5;

Tim Ward14; Adam Webb10; Catharine ML West7; Jenny Chang-Claude1,16;

Tiziana Rancati6

1German Cancer Research Center (DKFZ), Heidelberg, Deutschland

2Fundacion Publica Galega Medicina Xenomica, Santiago de Compostela,

Spanien

3ICM Institut du Cancer Montpellier, Montpellier, Frankreich

4Belgien

5Ghent University Hospital, Ghent, Belgien

6Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italien

7The University of Manchester, Manchester, Vereinigtes Königreich

8Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spanien

9UZ Leuven, Leuven, Belgien

10University of Leicester, Leicester, Vereinigtes Königreich

11Mount Sinai School of Medicine, New York, USA

12Maastro Clinic, Maastricht, Niederlande

13Universitätsmedizin Mannheim, Mannheim, Deutschland

14Vereinigtes Königreich

15University of Milan, Milan, Italien

16University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

Background: To prospectively assess the course of health-related quality

of life (HRQoL) and fatigue in a multicentre cohort of men with prostate

cancer (PCa) up to ve years aer radiotherapy (RT).

Methods: Adult men with non-metastatic PCa were recruited 2014-2016

prior to start of RT (external beam and/or brachytherapy according to

local standard of care; +/- hormonal treatment [HT], +/- prostatectomy)

into the multicentre international observational REQUITE study (www.

requite.eu). Data on HRQoL was prospectively collected using EORTC

QLQ C30 at multiple time points between pre-RT baseline (BL, N=1,714)

and 5 years aer RT (N=496). So far, 1,495 men completed at least one

post-RT survey 2-5 years aer RT. Global health status/QoL and the

fatigue domain were analysed.

Result: Global HRQoL scores declined from mean scores of 74.9 at BL to

69.9 at the end of RT. One year aer RT, the mean scores returned to BL

levels and remained stable until 5 years. Fatigue levels peaked at the end

of RT (26.6 vs. 17.3 at BL) and returned to BL levels aerwards. Fatigue

scores varied signicantly by country. Patients with HT reported higher

mean fatigue levels than patients without (p<0.05, BL through 2 years).

Severe fatigue (i.e. above the threshold for clinical importance of >=39;

PMID: 31639445) was reported by 11%, 23%, 15%, and 11% of the men

at BL, end of RT, at 2 years and at 5 years, respectively. 25% and 35% of

men experienced a deterioration of HRQoL or fatigue (change of >= 10;

median age of 70/71, respectively, vs. 68 without deterioration), respec-

tively, when comparing 5-year scores to BL.

Discussion: e long-term follow-up is still ongoing (RADprecise/

REQUITEplus projects) and multivariate models accounting for rele-

vant co-variates using updated data will be presented at the congress and

will identify the impact of treatment versus general health related factors

including age.

Conclusion: Despite good overall HRQoL, long-term survivorship care

for men with PCa should routinely include patient reported outcome mea-

sures as an important tool to identify unmet health needs (e.g. fatigue).

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts214

Poster

Feasibility and safety of exercise with patients suering

from advanced pancreatobiliary cancers(aPBC) receiving

beyond rst-line chemotherapy with and without exercise

therapy (P-Move)

Nico De Lazzari1; Miriam Götte2; Freerk T. Baumann3; Timo Niels3;

Martin Schuler1,4; Jörg Hense1; Stefan Kasper-Virchow1; Mitra Tewes1,

Jens Siveke1,4,5

1Universitätsklinikum Essen, Westdeutsches Tumor Zentrum, Innere Klinik

(Tumorforschung), Essen, Deutschland

2Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin,

Kinderheilkunde III, Essen, Deutschland

3CIO - Centrum für Integrierte Onkologie Uniklinik Köln, Köln, Deutschland

4Deutsches Konsortium für Translationale Krebsforschung (DKTK),

Partnerstandort Universitätsklinikum Essen, Essen, Deutschland

5Institut für Experimentelle Tumortherapie, Westdeutsches Tumorzentrum,

Essen, Deutschland

Background: Patients (Pts) with advanced pancreatobiliary cancers

(aPBC) frequently suer from high symptom burden. Studies of curative

treatments indicate that exercise can reduce treatment side eects and

improve patient-related outcomes (PROMs). However, evidence from

prospective studies in the palliative settings is rare. e primary aim of

the prospective, randomized-controlled study P-MOVE is to evaluate the

feasibility of exercise therapy (ET) in patients with aPBC beyond rst-line

chemotherapy.

Methods: 40 Pt (Stage III/IV) will be recruited beyond rst-line therapy.

Pts are randomized according to the minimization procedure with strata:

gender, age and loss of body weight past six months. e intervention

group (IG) completes 3 training units per week for 8 weeks (1x super-

vised strength training, 2x individualized home-based trainings weekly).

Control group (CG) receives recommendations on daily activities.

Result: Since study initiation, 158 Pts were screened. Of those 126 Pts

did not meet eligibility criteria. Of 32 eligible Pts, 22 have been recruited

(68.7%). Reasons for not participating were distance to study center

(n=5), clinical deterioration or death during screening period (n=3) and

no interest in ET (n=2). e drop-out rate was 31.8% (4 in IG and 3 in C).

Main reasons for drop-out were reduced general condition due to disease

progression (n=5) and cancer-related death (n=1). Adherence to ET in

total was 132/168 (78.5%) and 86/112 (76.7%) for unsupervised ET ses-

sions. No adverse events related to ET were reported. Statistical compari-

son of PROMs will be provided with higher patient enrolment.

Discussion: Pts with aPBC are highly motivated to ET aer rst-line

chemotherapy but suer from high symptom burden. Drop-out rates are

comparable to other clinical trials studying ET in palliative cancer treat-

ment settings. Supervised ET oered twice weekly may be more ecient

to improve PROMs.

Conclusion: Preliminary data suggest that ET beyond rst-line palliative

treatment in Pts with aPBC appears feasible and safe yet challenging.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Patient-reported outcome measurement (PROM) of the

health-related quality of life of patients with supercial

urothelial carcinoma of the urinary bladder

Desiree Louise Dräger; Benedikt Kunz; Laila Schneidewind;

Julia Nolting; Oliver Hakenberg

Klinik und Poliklinik für Urologie, Universitätsmedizin Rostock, Rostock,

Deutschland

Purpose: Bladder carcinoma is the second most common tumor dis-

ease in urology. e supercial variant is characterized by a high rate of

recurrence, so that close follow-up care is necessary, which inuences the

quality of life. A supplementary module to the EORTC-QLQ-C30, the

QLQ-NMIBC-24, is currently available for examining the health-related

quality of life (QoL) in supercial bladder cancer. e aim of the study

was to measure the patient-reported outcome of the QoL of patients with

supercial bladder carcinoma.

Material: Evaluation of patients with supercial bladder cancer (n = 141)

using EORTC-QLQ-C30 and -QLQ-NMIBC-24. ese provide informa-

tion about quality of life, functional scales (physical, emotional, cognitive,

social functioning and role function), general symptom scales, 6 individ-

ual items (including inappetence, insomnia) and cancer-specic function

and symptom scales (including voiding, sexuality).

Results: e examined patients showed poor emotional, social and role

function. ey also reported more frequent loss of appetite, fatigue,

insomnia and voiding problems. Patients who received intravesical instil-

lation therapy showed a poorer health-related QoL than patients without

intravesical relapse prevention.

Discussion: Patients with supercial bladder cancer have an impaired

quality of life. e so-called "response shi" must be taken into account,

which leads to shis within the function and symptom scales with con-

stant QoL, i.e. the priorities are rearranged with a time lag to the surgery.

Conclusions: e reduced quality of life in patients with supercial blad-

der cancer must be considered in the follow-up care by the attending phy-

sician and alternative solutions must be oered if necessary.

Disclosure Statement: e authors declare no conict of interest.

232

Severity of postprostatectomy urinary incontinence and

quality of life

Marc Heydenreich; Dirk-Henrik Zermann

Vogtland-Klinik Bad Elster, Bad Elster, Deutschland

Background: Postoperative urinary incontinence has major eects on

psychosocial health. e aim of the study was to examine what inuence

the early continence situation has on the health-related quality of life

(QoL) of patients aer radical prostatectomy.

Methods: 92 patients (Ø 64.0 years) aer radical prostatectomy took

part in the study. e health-related Quality of life (FACT-G) and pros-

tate-specic functional restrictions (FACT-P) were assed using a ques-

tionnaire (Functional Assessment of Cancer erapy) at the beginning of

a follow-up rehabilitation (mean - 14.8 days p.o.). e severity of urinary

incontinence was evaluated with the 1-hour pad test.

Result: severity of urinary incontinence <=10g (n=50):

physical well-being=24.1 (3.6); functionality=19.4 (5.1); FACT-P=32.9

(5.6); mental well-being=19.9 (3.3)

severity of urinary incontinence >=11g (n=42):

physical well-being=22.5 (3.3); functionality=18.4 (5.4); FACT-P=29.1

(6.7); mental well-being=20.2 (3.3)

p-value within the group aer 21 days of rehabilitation:

physical well-being=0.03; functionality=0.69; FACT-P=0.003; mental

well-being=0.35

Discussion: ere are signicant QoL dierences in physical well-being

and in FACT-P between low and higher amounts of urine loss.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 215

Conclusion: e study results show that the health-related quality of life

(physical well-being, FACT-P questionnaire) is negatively inuenced in

patients with greater urine loss (> 50g / 1-h pad test). Accordingly, in

addition to therapeutic treatment of urinary incontinence, these patients

should receive urological advice and psychological support.

Disclosure Statement: e authors declare no conict of interest.

288

Inuence of side eects of therapy on quality of life and

treatment satisfaction of gynecological cancer patients in

BNGO practices in Germany in 2020

Jörg Schilling; Beatrice Schröder; Petra Ortner

BNGO e.V., Neuenhagen, Deutschland

Background: To ensure the quality of outpatient care for patients (pts.)

with gynecological malignancies in BNGO practices and to evaluate the

quality of life of the patients and physical and psychosocial burden and

stress caused by the therapy, the BNGO has been conducting surveys

among patients who are cared for in BNGO practices since 2012. e last

survey took place from February to July 2020.

Methods: e NCCN distress thermometer was used by the patients to

evaluate the general stress caused by the therapy in the past week. e fre-

quency of symptoms and side eects during therapy as well as long-term

side eects and the use of complementary measures were documented

in patient diaries. Side eects and stress caused by chemotherapy in the

patients who received chemotherapy were recorded separately.

Results: By February 2021, 1,853 patient questionnaires have been

returned from 46 practices e most common problems and those per-

ceived as most stressful by all patients irrespective of therapy modality

were sleep disorders, followed by tiredness/exhaustion, numbness/tin-

gling in the extremities and bone and muscle pain. Alopecia was a signif-

icant problem in chemotherapy patients and was much distressing for the

respective patients.

Discussion: Sleeping disorders, fatigue, exhaustion and bone and muscle

pain were the most distressing side eects in all patients independently of

therapy mode. Alopecia, peripheral neuropathy and nausea were the most

distressing side eects in chemotherapy patients.

Conclusion: Like in the last surveys, the patients were highly satised

with the treatment in BNGO practices. Overall, 98% of patients would

choose outpatient treatment again and 99.5% would return to the same

practice.

Disclosure Statement: e authors declare no conict of interest.

299

Study Protocol of a Randomized Controlled Trial:

Argentine Tango for Breast Cancer Patients with Fatigue

Shiao Li Oei1; Anja Thronicke1; Thomas Rieser2; Sarah Becker3;

Jessica Groß3; Harald Matthes1,4,5; Friedemann Schad1,5

1Forschungsinstitut Havelhöhe gGmbH am Gemeinschaftskrankenhaus

Havelhöhe, Berlin, Deutschland

2Charite-Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt-Universität zu Berlin, Institut für Sozialmedizin,

Epidemiologie und Gesundheitsökonomie, Berlin, Deutschland

3Gemeinschaftskrankenhaus Havelhöhe Frauenheilkunde und Geburtshilfe,

Brustkrebszentrum, Berlin, Deutschland

4Medical Clinic for Gastroenterology, Infectiology and Rheumatology CBF,

Charite-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin

and Humboldt-Universität zu Berlin, Institut für Sozialmedizin, Epidemiologie

und Gesundheitsökonomie, Berlin, Deutschland

5Gemeinschaftskrankenhaus Havelhöhe Interdisziplinäre Onkologie und

Palliativmedizin, Berlin, Deutschland

Background: Many breast cancer patients suer from persistent impair-

ment, particularly cancer-related fatigue (CRF), which severely impacts

their quality of life. e purpose of this study is to investigate whether a six

week tango module is suited as a therapeutic approach for breast cancer

patients to favorably inuence their quality of life, especially fatigue levels.

Methods: Sixty breast cancer patients with fatigue, diagnosed 12-48

months before enrollment with cancer stage I-III are recruited and ran-

domized 1:1 to a tango or a waiting-list group. Movement concepts using

elements of Argentine tango, which are oriented towards walking in music,

self- and spatial perceptions are examined with the participants during

six weekly 60 min tango sessions. e primary outcome is the improve-

ment of fatigue (German version of the Cancer Fatigue Scale). Secondary

outcomes are the improvement in sleep quality (Pittsburgh Sleep Quality

Index) and quality of life (EORTC-QLQ-C30). Patient reported outcomes

are measured at baseline and six weeks later and an evaluation will be

performed by means of descriptive data analysis.

Result: It is anticipated that aer the six-week tango module CRF, sleep

and quality of life scores will improve. First results will be presented.

Discussion: To counter fatigue symptoms, exercise and physical activity

are recommended as rst-line interventions, and mind-body and music

therapies have also been shown to be eective in reducing stress. Tango

therapy that combines various elements may therefore have benecial

eects in breast cancer patients.

Conclusion: It is expected that physical, psychological, and cognitive

skills could be supported with Argentine tango in breast cancer patients.

A follow-up evaluation will reveal how this tango module is perceived by

the participants and how lasting the eects will prove to be.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

456

Introducing SKINFO – the new and unique web-based

information platform for German-speaking skin cancer

patients

Theresa Steeb1; Julia Homann2; Friedegund Meier2; Christiane Weber3;

Maike Bergmann2; Anne Müller-Schuchardt2; Nina Weiler4;

Astrid Doppler5; Carola Berking1; Dirk Schadendorf6

1Hautklinik, Universitätsklinikum Erlangen, Erlangen, Deutschland

2Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus

Dresden, Dresden, Deutschland

3MEDEA GmbH Medical Education Academy, Saarbrücken, Deutschland

4Eurice - European Research and Project Oce GmbH, Sankt Ingbert,

Deutschland

5Melanom Info Deutschland - MID e.V., Essen, Deutschland

6Universitätsklinikum Essen Hautklinik, Essen, Deutschland

Background: e incidence of skin cancer has been rising steadily for

years. An increasing need for reliable information has been observed

among patients, as being informed about the disease is an integral part for

informed decision-making. e Internet represents the most important

source to acquire disease-related information. However, web-based infor-

mation for skin cancer patients was previously found to be of insucient

quality.

Methods: An interdisciplinary team of dermato-oncologists, health care

scientists, patient representatives and communication experts developed

the website in a multi-step process. Following this, usability tests were

conducted to identify problems and to optimize the website’s rst dra.

Importantly, the content of the website as well as externally available

sources (videos, brochures) will be continuously reviewed by all relevant

stakeholders using evidence-based criteria, i.e. medical experts will check

the correctness, health care scientists the reliability and patient represen-

tatives evaluate the relevance.

Result: SKINFO (www.infoportal-hautkrebs.de) has been launched in

02/21 and addresses German-speaking skin cancer patients, their relatives

and interested parties. e website provides high quality and reviewed

information on common and less common skin cancer entities as well as

information on further patient-related topics, i.e. psychosocial support,

nance or lifestyle. Usability testing revealed that the website’s layout, nav-

igation and content need optimization.

Discussion: SKINFO is the rst web-based platform including common

and less common skin cancer entities and relevant topics with high qual-

ity and reviewed information. Physicians may recommend SKINFO as it

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts216

represents an easily accessible, up-to-date and reliable source of informa-

tion. Further usability tests will be performed in order to optimize the

website.

Conclusion: e unique web-based information platform has the poten-

tial to enable patients and their relatives to cope with skin cancer and thus,

strengthen informed decision-making.

Disclosure Statement: e authors declare the following:

Honorare für Vorträge und Beratertätigkeiten

471

Perspectives and concerns of German women with an

increased hereditary risk for breast and ovarian cancer

regarding infection-specic risks and cancer-specic risks

during the SARS-CoV-2 pandemic: Results of a cross-sectional

web-based survey

Roxana Schwab; Annika Droste; Annette Hasenburg

University Medical Center Mainz, Department of Gynecology and Obstetrics,

Mainz, Deutschland

Background: e SARS-CoV-2 pandemic has aected the entire world,

but some subgroups of patients have been disproportionally aected.

Cancer patients showed a higher prevalence of COVID-19 disease, as well

as a higher incidence of severe COVID-19 illness and higher death rates

from COVID-19.

Methods: To assess the perspectives and believes of women with an

increased hereditary risk for breast (BC) and ovarian (OC) cancer regard-

ing infection-specic and cancer-specic risks during the SARS-CoV-2

pandemic, a web-based survey was placed on internet platforms of sup-

port groups between 29th January and 22th April 2021. Data are presented

as frequencies of selected items. Correlations were assessed by non-

parametric tests.

Result: Asked about their concerns to face a more severe disease course

of COVID-19 illness, 44.2% responded, they were not concerned, while

27.3% were more concerned and 23.4% were signicantly more con-

cerned. Higher concerns were correlated with higher age (p=0.001) and

were associated with a positive history of invasive breast cancer (p=0.001).

When asked about concerns of being at higher risk for occurrence of

breast and ovarian cancer aer being infected with SARS-CoV-2, 72.7%

reported no concerns, while 11.7% reported moderate concerns and 5.2%

had signicant concerns. Higher concerns were correlated with higher age

(p<0.047), while higher resilience was a protective factor (p=0.029)

ose with a positive medical history for in situ or invasive BC or OC were

asked about concerns regarding an unfavorable oncological outcome as a

result of an infection with SARS-CoV-2. 23.0% had no concerns, while

24.3% had moderate increased concerns and 14.9% reported signicantly

increased concerns.

Discussion: Age proved to be a risk factor for health-related worries

during the COVID-19 pandemic, while higher resilience proved to be

protective to health-related concerns.

Conclusion: Patients with additional risk factors may be at risk to experi-

ence health-related worries and anxiety, and should be monitored closely.

Disclosure Statement: e authors declare the following:

RS: Honoraria: Roche Pharma AG, AstraZeneca, Streamedup!GmbH, AH: Hono-

raria: AstraZeneca; Celgen; MedConcept GmbH, Med update GmbH; Medicultus;

Pzer; Promedicis GmbH; Soconsult; Roche Pharma AG; Streamedup!GmbH;

Tesaro Bio Germany GmbH, LEO Pharma

532

Clinical and sociodemographic determinants of disease-

specic health-related quality of life in long-term breast

cancer survivors

Daniela Doege1; Melissa Thong1; Lena Koch-Gallenkamp2; Heike Bertram3;

Andrea Eberle4; Bernd Holleczek5; Alice Nennecke6; Ron Pritzkuleit7;

Annika Waldmann8; Sylke Ruth Zeissig9; Hermann Brenner2,10,11;

VolkerArndt1

1German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and

Aging Research, Cancer Survivorship, Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and

Aging Research, Heidelberg, Deutschland

3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland

4Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen

Cancer Registry, Bremen, Deutschland

5Saarland Cancer Registry, Saarbrücken, Deutschland

6Hamburg Cancer Registry, Hamburg, Deutschland

7Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland

8University Lübeck, Institute of Social Medicine and Epidemiology, Lübeck,

Deutschland

9Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland

10German Cancer Research Center (DKFZ), Division of Preventive Oncology,

Heidelberg, Deutschland

11German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK),

Heidelberg, Deutschland

Background: It is important to monitor disease-specic issues of breast

cancer survivors (BCS) to be aware of potential unmet supportive care

needs. Most studies on disease-specic health-related quality of life

(HRQoL) in BCS had small samples, low cancer stages, or limited to

short-term survivors, certain age ranges or treatments. Our study aims

to address gaps of previous studies, by using a large, population-based

cohort of long-term BCS (5-15 years post-diagnosis), including a broad

range of ages, stages and treatments.

Methods: e sample of 3045 BCS (age 30-89 years) was recruited

in a German multi-regional population-based study (CAESAR+).

Disease-specic HRQoL was assessed by the European Organization

for Research and Treatment of Cancer Breast Cancer-Specic Quality of

Life Questionnaire (EORTC QLQ-BR23). Dierences in HRQoL were

assessed with multiple regression, adjusted for age, education, time since

diagnosis, stage, recurrence, and self-reported treatments (operation, che-

motherapy, endocrine therapy, radiotherapy, lymph node dissection).

Result: Body image and future perspective increased with age, whereas

sexual functioning decreased with age. At 30-49 years, women who had

breast-conserving therapy or mastectomy with breast reconstruction (BR)

reported a better body image compared to those who had mastectomy

alone. At 50-79 years, there was no dierence according to mastectomy

with/without BR. In specic age groups, lymph node dissection and radio-

therapy were associated with arm and breast symptoms, and chemo- and

endocrine therapy were associated with worries about hair loss. Disease-

free BCS aged 30-79 years reported a better future perspective than those

who reported any metastasis, recurrence or second cancer.

Discussion: Disease-specic HRQoL in long-term BCS was mainly

age-dependent. Nevertheless, in some subgroups, treatment-associated

symptoms were found long aer diagnosis.

Conclusion: Vulnerable BCS should be monitored longitudinally.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 217

617

Evaluationofthe 12-week exercise interventionYOUEX on

quality of life and fatigue inyoung adults with cancer

Annelie Voland1,2; Miriam Götte3; Verena Krell4; Maximilian Köppel1,2;

Timo Niels5; Inaam El-Rajab1,2; Joachim Wiskemann1,2

1Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

2Universitätsklinikum Heidelberg, Heidelberg, Deutschland

3Universitätsmedizin Essen, Zentrum für Kinder- und Jugendmedizin, Essen,

Deutschland

4Charité - Universitätsmedizin Berlin, Abteilung Sportmedizin, Berlin,

Deutschland

5Uniklinik Köln, Centrum für Integrierte Onkologie (CIO) Köln, Köln, Deutschland

Background:Anoverwhelming body of scientic evidencedisplays the

positive eects of physical activity for cancer patients.However, infor-

mation about the ecacy of digital exercise programs to ameliorate

tumor-therapy-relatedside eectssuch as cancer related fatigue (CRF)

and health related quality of life (QoL)for young adults with cancer is

scarce.

Objective:e aim of this study is to analyze the impact of a 12-week

exercise interventionon CRF andtheQoLin young cancer patients (18–

39 years).

Methods: We recruited patients who currently have or had a cancer

diagnosis within the past 5 years.Eligible patients chosebetween three

exercise modules (M1: social mediaexercise program, M2: independent

training via online-training platform, M3: participation in an in-per-

son community-based exercise program).e selected modulecouldbe

replaced or amended by another module aer 6weeks.Primary endpoints

were assessed by questionnaires (EORTC QLQ-C30 and QLQ-FA12)

atthreetime points (T0: baseline, T1: aer 6 weeks intervention; T2: aer

12 weeks intervention).

Results: Within 8 months n=105 participants were recruited, and n=92

started the intervention. Mean age was 31.9 (± 4.85) years, 93.4% were

female, and 55.43% had a breast cancer diagnosis. Quality of life scales

physical functioning, social functioning, and emotional functioning

improved signicantly from baseline to T2 (all p<0.01), but global quality

of life did not change (56.8; 58.2). Fatigue, as measured with the QLQ-

C30 symptom scale signicantly improved from baseline to T2 (59.8;

50.4, p<0.0001), but not in the three fatigue scales as measured with the

QLQ-FA12.

Discussion:Global quality of life and fatigue as measured with the FA12

were reduced in the YOUEX group but did not change from baseline

to post-intervention. Although the study is lacking a control group, the

intervention seems to be eective to improve the functional dimensions

of quality of life.

Conclusion:Due to the discrepant results on fatigue, no clear statements

can be made on this at present and further analyses are required.

Disclosure Statement: e authors declare no conict of interest.

635

Development of tumor disease-specic PRO-CTCAE item sets

Maximilian Günther1; Theresa Müller2; Markus Schuler3,4;

Leopold Hentschel2; Katharina Schütte3; Yon-Dschun Ko5;

Ingo Schmidt-Wolf6; Ulrich Jaehde1

1Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn,

Deutschland

2University Cancer Centre (NCT/UCC), University Hospital Carl Gustav Carus

Dresden, Psychooncology, Dresden, Deutschland

3University Cancer Centre (NCT/UCC), University Hospital Carl Gustav Carus

Dresden, Dresden, Deutschland

4Onkologischer Schwerpunkt, Oskar-Helene-Heim Berlin, Berlin, Deutschland

5Department of Internal Medicine, Johanniter Hospital Bonn, Internistische

Onkologie, Bonn, Deutschland

6Department of Integrated Oncology, University Hospital Bonn, Bonn,

Deutschland

Background: In oncology, adverse events (AE) are documented using the

Common Terminology Criteria for Adverse Events (CTCAE)1. is phy-

sicians-reported assessment can be supported by patient-reported out-

comes (PRO)2. For this reason, the NCI has developed a PRO version of

the CTCAE criteria, consisting of a pool of 78 symptoms and 124 items3.

A core item set containing 31 items for patients with chemotherapy has

already been validated in German4.

e aim of this study was to develop tumor disease-specic PRO-

CTCAE item sets for dierent tumor entities with high content validity.

Methods: Patients treated at three outpatient centres were asked to assess

the occurrence and relevance of the 78 PRO-CTCAE symptoms using

a questionnaire. In order to select PRO-CTCAE items for each tumor

entity, individual symptoms were ranked on the basis of occurrence and

relevance.

Result: 101 patients with breast cancer (BC), 107 with multiple myeloma

(MM) and 66 with prostate cancer (PC) were analysed. e BC item set

contains 21 symptoms, the MM and PC item set each 19 symptoms. 8

symptoms are included in all three item sets. e symptoms with the

highest rankings across the item sets were fatigue and sleep disorders.

Symptoms with the highest rankings included only in one item set were

symptoms aecting the urogenital system in the PC item set, blurred

vision in the BC item set and appetite loss in the MM item set.

Conclusion and Outlook: Based on patient-reported dierences in symp-

tom pattern, specic PRO-CTCAE item sets with high content validity

were developed for BC, MM and PC. In order to validate the quality and

psychometric criteria of the new item sets further studies are required.

e validation of the PRO-CTCAE-MM item set is currently ongoing in

a multicentre, one-time survey using a browser-based app. Within the

survey patients complete the PRO-CTCAE-MM item set and the corre-

sponding EORTC questionnaires.

Indication of source:

1 NCI. CTCAE Version 5.0. 2017

2 Basch E. N Engl J Med 2010; 362: 865-869

3 Basch E et al. J Natl Cancer Inst 2014; 106: 1-11

4 Hagelstein V et al. Ann Oncol 2016; 27: 2294-2299

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts218

898

Prognostic potential of baseline HRQoL in advanced and

metastatic renal cell carcinoma

Viktor Grünwald1; Peter J. Goebell2; Martin Schostak3; Manfred Welslau4;

Christian Doehn5; Elisa Degenkolbe6; Rainer Ehneß6; Kerstin Ahrens7;

Martin Bögemann8

1Universitätsklinikum Essen, Westdeutsches Tumorzentrum Essen, Innere Klinik

(Tumorforschung) und Klinik für Urologie, Essen, Deutschland

2Universitätsklinikum Erlangen, Urologische Klinik, Erlangen, Deutschland

3Otto-von-Guericke-Universität Magdeburg, Klinik für Urologie, Uroonkologie,

Robotergestützte und fokale Therapie, Magdeburg, Deutschland

4Klinikum Aschaenburg-Alzenau, Hämato-Onkologische Schwerpunktpraxis,

Aschaenburg, Deutschland

5Urologikum Lübeck, Lübeck, Deutschland

6Novartis Pharma GmbH, Novartis Oncology, Nuernberg, Deutschland

7APOGEPHA Arzneimittel GmbH, Dresden, Deutschland

8Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Münster,

Deutschland

Combinations of laboratory and clinical parameters complement each

other to risk scores such as IMDC. Well-established prognostic factors are

needed to predict patient’s outcome. e prognostic value of health-re-

lated quality of life (HRQoL) has been shown for various tumor entities.

Here, we report baseline QoL-values and their prognostic potential for

renal cell carcinoma (RCC) patients.

In the prospective, non-interventional PAZOREAL study, 376 RCC

patients were treated with pazopanib in rst line and other antineoplastic

agents (i.e., nivolumab, everolimus), subsequently. HRQoL was evaluated

with ve-dimensional EuroQol EQ-5D-5L questionnaire in 279 patients.

Five dimensions comprising mobility, self-care, usual activities, pain/dis-

comfort and anxiety/depression are rated by a 5-digit-scale. Out of this,

a single value index called baseline utility score (BUS) was calculated

non-parametrically. Self-rated health was reported by visual analogue

scale (VAS) at baseline. Both, VAS and BUS, were categorized into four

subgroups: poor, low-intermediate (med-low), high-intermediate (med-

high) and good according to its quartiles.

e median VAS at baseline was 70 with lower (25%) and upper (75%)

quartiles at 50 and 80, respectively. Median BUS was 0.9 with quartiles at

0.716 and 0.918. Median overall survival (mOS) diered in the subgroups

between 14.7 months (poor), 30.1 months (med-low), 48.3 months (med-

high) and 53.6 months (good). For patients with poor BUS, mOS was 14.8

months, whereas mOS for med-low, med-high and poor BUS was 53.6,

43.4 and 41.5 months, respectively. Linear regression analysis of OS with

each score revealed a signicant correlation with R=0.22.

Addition of baseline HRQoL might improve prognostic tools to pre-

dict RCC patient’s outcome. However, only one score should be consid-

ered for further analysis. Although correlation of OS with VAS or BUS is

comparably low, VAS tends to separate dened subgroups more precisely.

us, our data indicate that VAS score is more suitable as additional prog-

nostic marker in RCC patients.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

905

Patient needs and wishes in cancer therapy - online survey

with cancer patients

Beke Freyer1; Helen Beckmann2; Christine Blome1

1Institut für Versorgungsforschung (IVDP), Hamburg, Deutschland

2AstraZeneca GmbH, Wedel, Deutschland

Background: Cancer impacts patients’ quality of life (QoL) severely.

erefore, it is important to include the patients’ perspective in cancer

research and treatment. is study aimed to analyze patients’ view on

their cancer therapy and the evaluation of their recovery.

Methods: 248 participants with dierent cancer types (mainly breast,

prostate, lung and ovarian) lled in online questionnaires in 2020. Most

questions were quantitative, covering the topics QoL, cancer recovery and

the patients’ view on their therapy. Several qualitative questions covered

topics such as feeling recovered. e quantitative results were analyzed

with descriptive methods using IBM SPSS Statistics, the qualitative results

were coded with inductive categories.

Result: e mean age of patients was 60.9 years, 61.7% were female

(n=153). Most participants had undergone surgery as a treatment for their

cancer (n=204), 147 patients had received radiation therapy and 122 had

received chemotherapy.

In the therapy, the most important aspect for patients was the best

possible QoL, followed by longest possible survival; having longest pos-

sible therapy free period was the least important aspect in all subgroups.

Most patients felt well involved in therapy decisions; men reported they

had been presented with more options by their doctor than women.

Chances of recovery were overall rated as rather good (arithmetic mean of

5.61; Likert-scale 1 to 7). Reasons why patients did not yet feel recovered

included the physical impact of the cancer, the fear to experience a relapse,

and others.

Discussion: Having the best possible QoL seems to be the most import-

ant aspect in cancer therapy for patients. Even though patients mostly

received only one therapy option by their doctor, they feel well involved

in the therapy decisions.

However, due to the heterogeneity of the population and the small sample

size of subgroups, results have to be interpreted with caution.

Conclusion: e patient perspective is crucial and needs to be included

in the cancer treatment planning as the QoL is the most important aspect

during the therapy.

Disclosure Statement: e authors declare the following:

Projekt gesponsert von AstraZeneca GmbH

909

Prostate Cancer Patient Reported Outcome After Cyberknife

Robotic Radiosurgery

Sebastian Exner; Felix Behrens; Fabian Fehlauer

1Strahlenzentrum Hamburg MVZ, Hamburg, Deutschland

Background: e optimal management of localized Prostate Cancer (PC)

should take account consideration of patient and clinical risk factors. e

objectives of this cohort study of men with newly diagnosed localised PC

were to document side eects with the International Prostate Symptom

Score (IPSS), International Consultation on Incontinence Questionnaire

Short Form (ICIQ-SF), International Index of Erectile Function

Questionnaire (IIEF-5) and as well Patient-Reported Outcomes version

of the Common Terminology Criteria for Adverse Events Questionnaire

(PRO-CTCAE) following radiosurgery with the Cyberknife.

Methods: In this cohort analysis, 40 patients with localized PC were

analyzed who received Cyberknife radiosurgery (5 x 7,25 Gy) and com-

pleted the IPSS, ICIQ-SF, IIEF-5 and the German validated PRO-CTCAE

questionnaires.

Result: Mean IPSS score was 6.9 (mild symptomatic), mean ICIQ-SF score

was 3.3 (mild impairment of incontinence), mean IIEF-5 score was 17.0

(mild erectile dysfunction). e highest score at PRO-CTCAE was for

urinate frequency (two patients, 5%), achieve and maintain erection (two

patients, 5%), ejaculation problems (four patients, 10%) and decreased

libido (two patients, 5%). ere was no signicant dierence at follow-up

period or treated prostate volume (F/U: > 1 vs. < 1 year; Volume ml: >64

vs. <64). Local control and overall survival were 100%.

Discussion: e local control of the radiosurgery was with longer fol-

low-up periods persistently very high with low toxicity. In particular, the

late toxicity appears to be lower than with surgery or conventional exter-

nal radiation. Since curative therapy options in man with localized PC

remain iso- eective, it is important to choose a treatment strategy with a

low impact on the health-related quality of life and high cure rate.

Conclusion: Radiosurgery for localized PC shows good local control and

overall survival with a very mild side eect reported by patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 219

968

Improved quality of life (QOL) with lisocabtagene

maraleucel (liso-cel), a CD19-directed chimeric antigen

receptor T cell therapy, compared with standard of care (SOC)

using salvage chemotherapy (CT) followed by autologous

stem cell transplantation (ASCT) as second-line (2L) treatment

in patients (pt) with relapsed or refractory (R/R) large B-cell

lymphoma (LBCL): results from the phase 3 TRANSFORM study

Bertram Glaß1; Jeremy Abramson2; Patrick B Johnston3; Manali Kamdar4;

Sami Ibrahimi5; Koji Izutsu6; Jon Arnason7; Pim Mutsaers8;

Matthew Lunning9; Julia Braverman10; Fei Fei Liu10; Alessandro Crotta11;

Sandrine Montheard11; Alessandro Previtali11; Shien Guo12;

Ling Shi12; Scott Solomon13

1Helios Klinikum Berlin-Buch, Berlin, Deutschland

2Massachusetts General Hospital Cancer Center, Massachusetts, USA

3Mayo Clinic, Jacksonville, USA

4University of Colorado Cancer Center, Colorado, USA

5University of Oklahoma Stephenson Cancer Center, Oklahoma, USA

6National Cancer Center Hospital, Tokyo, Japan

7Beth Israel Deaconess Medical Center, Boston, USA

8Erasmus University Medical Center, Rotterdam, Niederlande

9University of Nebraska Medical Center, Omaha, USA

10Bristol Myers Squibb, New York, USA

11Celgene, a Bristol-Myers Squibb Company, Zürich, Schweiz

12Evidera, Seattle, USA

13Northside Hospital Cancer Institute, Atlanta, USA

Background: Pts with previously treated R/R LBCL have compromised

health-related QOL (HRQOL). Here we present pt-reported outcomes

(PRO) from TRANSFORM.

Methods: TRANSFORM is a pivotal, randomized, phase 3 study compar-

ing liso-cel vs SOC (3 cycles of salvage CT then ASCT in responders) in

adults (18–75 y) with R/R LBCL ≤ 12 mo aer rst-line therapy intended

for ASCT. Crossover to liso-cel was allowed in the SOC arm. e EORTC

QLQ-C30 and FACT-LymS were administered at randomization (baseline

[BL]) and on Day (D) 29 (liso-cel infusion or 2 cycles of salvage CT), 64

(1 mo aer liso-cel or CT completion), and 126 (3 mo aer liso-cel or 2

mo aer ASCT), and at Mo 6. No PRO data were collected aer crossover.

Global health/QOL (GH/QOL), physical functioning, cognitive function-

ing, fatigue, pain, and FACT-LymS were the primary domains of inter-

est. Prespecied thresholds dened clinically meaningful score changes.

A linear mixed model for repeated measures (MMRM) analysis assessed

dierences in least squares (LS) mean change from BL up to D126. All

analyses were descriptive.

Result: Of 184 randomized pts, 90 (49%) and 85 (46%) pts, respec-

tively, completed the EORTC QLQ-C30 (liso-cel vs SOC, n = 47 vs 43)

and FACT-LymS (n = 45 vs 40). In MMRM analyses, liso-cel tended

toward more favorable overall LS mean changes up to D126 vs SOC in

most domains. In particular, dierences in cognitive functioning (2.21

vs −2.09) and fatigue (−1.95 vs 3.75) for liso-cel vs SOC, respectively,

exceeded prespecied minimal important dierence thresholds. In indi-

vidual-level analyses, the proportions with meaningful deterioration in

fatigue and GH/QOL were lower for liso-cel vs SOC from BL to Mo 6.

At Mo 6, a lower proportion had worsened fatigue (18% vs 71%) and a

higher proportion had improved fatigue (47% vs 29%) for liso-cel vs SOC;

for GH/QOL, a lower proportion worsened (18% vs 57%) and a higher

proportion improved (53% vs 14%), respectively.

Discussion: Most primary HRQOL domains were more favorable in

liso-cel- vs SOC-treated pts.

Conclusion: ese data support use of liso-cel as 2L therapy in pts with

R/R LBCL.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

1049

Geruchs- und Geschmacksveränderungen beeinträchtigen

Krebspatienten mit Chemotherapie – eine prospektive

longitudinale nicht-interventionelle Studie

Tobias Bleumer1; Clara Kalweit1; Wolfgang Böhmerle2,3; Thomas Hummel4;

Sebastian Stintzing1; Lars Uwe Stephan1; Uwe Pelzer1

1Department of Hematology, Oncology and Tumorimmunology, Charité

Campus Mitte, Charité -Universitätsmedizin Berlin, Corporate Member of Freie

Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health,

Berlin, Deutschland

2Department of Neurology, Charité Campus Mitte, Charité - Universitätsmedizin

Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu

Berlin, and Berlin Institute of Health, Berlin, Deutschland

3Charité - Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin and Humboldt Universität zu Berlin, NeuroCure Cluster of Excellence,

Berlin, Deutschland

4Department of Otorhinolaryngology, Smell and Taste Clinic, Technische

Universität Dresden, Dresden, Deutschland

Introduction: Taste and smell alterations (TSA) are common side eects

in cancer patients undergoing chemotherapy. However, the connection

between specic malignancies and their corresponding chemotherapeutic

substances with TSA remains unclear. Also, longitudinal investigations

of TSA with both subjective and objective methods are scarce. e aim

of this study is to investigate TSA and its eects on cancer pts regarding

anorexia, weight loss, reduced quality of life (QOL) and the possible asso-

ciation with neuropathy.

Methods: Patients starting palliative or curative chemotherapy will be

surveyed and examined up to ve times (T0-T4). As of March 31, 2022,

50 out of 100 patients have been investigated. Clinical assessment is con-

ducted using psychophysical methods (Snin’ Stick and Taste Strips),

questionnaires, and electrophysiological examination. Development

of TSA and correlation with clinical and sociodemographic parame-

ters were analyzed using the Friedman-Test, Mann-Whitney-U-Test, or

Spearman-Correlation.

Results: Olfactory and gustatory function dropped 18.2% and 22.4%

between baseline and T1 ( p= 0.003 for both). ere was no signicant

TSA between T1 and T2, however (p= 0.377 and p= 0.45). Although poly-

neuropathy scores increased signicantly between T0 and T2 (p= 0.005),

the Mann-Whitney-U test only showed a tendency in relationship to

TSA so far (p= 0.095). Further analyses showed signicantly greater BMI

reduction and loss of appetite in patients experiencing stronger olfactory

dysfunction between T0 and T1 (p= 0.04 andp= 0.02, respectively). No

signicant changes were shown when grouped by gustatory dysfunction.

Full recruitment is expected in September 2022.

Conclusion: is rst set of data shows the extensive eect of TSA in

cancer patients undergoing chemotherapy. Aer analyzing the complete

data set, we dene dependencies between TSA, specic entity and therapy

more precisely in order to discuss therapeutic consequences and possible

prevention strategies, which will then form the basis for interventional

follow-up studies.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts220

Radiation

Best-of-Abstract-Vortrag

522

First analysis of the phase IV studyTARGIT B(oost) Q(uality)

R(egistry) using intraoperative radiotherapy as anticipated

boost in breast cancer patients

Elena Sperk1; Christel Weiss2; Robert Schnaubelt3; Uta Kraus-

Tiefenbacher4; Viktoria Brück5; Lelia Bauer6; Stefan Dinges7;

Albert von der Assen8; Christina Kaiser9; Heidrun Meye10;

Benjamin Tuschy11; Sebastian Berlit11; Marc Sütterlin11; Michael Ehmann1;

Ahmed Yasser Abou-Madian1; Katharina Fleckenstein1; Frank Schneider1;

Sven Clausen1; Frederik Wenz12

1Universität Heidelberg, Universitätsmedizin Mannheim, Medizinische Fakultät

Mannheim, Klinik für Strahlentherapie und Radioonkologie, Mannheim,

Deutschland

2Universität Heidelberg, Universitätsmedizin Mannheim, Medizinische Fakultät

Mannheim, Biostatistik, Mannheim, Deutschland

3Lukaskrankenhaus Neuss GmbH, Medizinisches Versorgungszentrum, Neuss,

Deutschland

4Krankenhaus Nordwest, Radioonkologie, Frankfurt am Main, Deutschland

5Asklepios Klinik Barmbek, Brustzentrum, Hamburg, Deutschland

6GRN-Klinik Weinheim, Brustzentrum, Weinheim, Deutschland

7Städtisches Klinikum Lüneburg gemeinnützige GmbH, Klinik für

Strahlentherapie und Radioonkologie, Lüneburg, Deutschland

8Niels-Stensen-Kliniken Franziskus-Hospital Harderberg , Brustzentrum,

Georgsmarienhütte, Deutschland

9Universitätsfrauenklinik Bonn, Abteilung für Senologie/zertiziertes

Brustzentrum, Bonn, Deutschland

10Gesundheit NordhessenMVZ, Fachbereich Strahlentherapie, Kassel,

Deutschland

11Universität Heidelberg, Universitätsmedizin Mannheim, Medizinische Fakultät

Mannheim, Frauenklinik, Mannheim, Deutschland

12Uniklinik Freiburg, Freiburg im Breisgau, Deutschland

Background: TARGIT BQR is a prospective multicenter phase IV study

to evaluate clinical outcome aer intraoperative radiotherapy (IORT) with

low kV x-rays used as an anticipated boost in combination with a standard

external beam radiotherapy of the whole breast (EBRT) in high-risk breast

cancer patients in a real world setting.

Methods: IORT was given immediately aer tumor resection with median

20 Gy in 1 fraction. Median RT time was 24 minutes. Median interval

between IORT and EBRT was 36 days. EBRT and systemic treatment

were given according to local standard/S3 recommendations. e study

was approved by the local Ethics Committee (2011-319N-MA) and is reg-

istered in clinicaltrials.gov (NCT01440010). All patients gave informed

consent. Statistical analyses were done with SAS, release 9.4.

Result: In total, 1133 patients from 10 centers in Germany were included

into the registry with 20.4% screening failure/drop out/missing data. IORT

boost was done in 90% and EBRT in 96%. Median FU was 32 months (1–

120) and median age 61 years (26–90). Risk factors were seen as follows:

22% N+, 23% >T1, 78% G2/3, 12% L1, 1% V1, 3% R1 and 10% Her2neu+.

Chemotherapy was given in 35% and 87% received endocrine therapy.

Postoperative erythema appeared in 4.9% and 10.7% had palpable seroma

with 0.4% requiring puncture. Wound healing disorder occurred in 2.3%.

Local recurrence occurred in 10 cases aer 12-55 months. Ipsi-/contralat-

eral tumor occurred in 2 and 3 patients aer 55 - 66 and 26-86 months,

respectively and metastasis in 14 cases aer 9-102 months. Overall 16 of

902 patients with at least 1 month FU (1.8%) died.

Discussion: is is the largest prospective data set with IORT as a boost

with low kV x-rays showing rst results with excellent clinical outcome.

Detailed toxicity data will be shown during presentation. Our data con-

rm previous retrospective single center analyses in a multicenter real

world setting in Germany.

Conclusion: IORT as a boost is a feasible method with excellent clinical

outcome.

Disclosure Statement: e authors declare no conict of interest.

584

Prophylactic cranial irradiation in extensive disease small cell

lung cancer

David Alexander Ziegler; Sonia Ziegler; Leif Hendrik Dröge; Martin Leu;

Sandra Donath; Manuel Guhlich; Markus Anton Schirmer;

Stefan Rieken

Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie

und Radioonkologie, Göttingen,

Background: e prot of prophylactic cranial irradiation (PCI) in

patients with extensive disease small cell lung cancer (ED-SCLC) is a con-

troversial topic. We performed a retrospective analysis of 89 patients in

order to evaluate the inuence of PCI on overall survival (OS).

Methods: Using data of our clinical information systems SAP, ixserv, ARIA

and oncostar we identied patients tagged as “SCLC” and “small cell lung

cancer”. All patients were included, who underwent radiation therapy

(RT) of at least one site except for brain metastases. Chi-squared test was

used to compare ECOG-status and rate of bone metastases between two

cohorts. Overall survival was calculated with Kaplan Meier estimator. e

signicance of the prognostic factors was veried with the log-rank test.

Result: Between 2007 and 2017, 89 patients with ED-SCLC with-

out brain metastases received RT in our institution. 63 of the 89

patients (70.8%) received PCI with fractionations of 10-15 x 2-3 Gy,

26 patients did not receive PCI. Mean age was 63.5 years in both

cohorts. In the PCI cohort, 25 patients (39.7%) were additionally

irradiated for pulmonary sites, 20 patients (31.8%) received addi-

tional bone irradiation. Within the patients without PCI, 13 patients

(50%) received thoracic RT and 17 patients (65.4%) bone RT.

ECOG-status was signicantly worse in patients without PCI. e rate of

bone RT diered signicantly between both cohorts. Mean OS was signi-

cantly better in the PCI cohort (6.8 months vs. 3.2 months).

Discussion: Patients with ED-SCLC without brain metastases receiving

PCI showed signicantly improved OS compared to patients without PCI.

In this retrospective study, ECOG-status and rate of RT of bone metasta-

ses were unbalanced, a selection bias cannot be excluded.

Conclusion: PCI in ED-SCLC leads to improved OS. Further prospective

studies are needed to verify these ndings.

Indication of source:

1 Ziegler, D. A., et al. DEGRO Jahrestagung 2021

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 221

Poster

Neoadjuvant chemoradiotherapy of cervical carcinoma

Leif Hendrik Dröge1; Manuel Guhlich1; Markus Schirmer1;

Laura Anna Fischer1; Sonia Ziegler1; David Alexander Ziegler1;

Stefan Rieken1; Stephanie Bendrich1

1Klinik und Poliklinik für Strahlentherapie und Radioonkologie,

Universitätsmedizin Göttingen (UMG), Göttingen, Deutschland

S Donath1; LH Dröge1; M Guhlich1; M Schirmer 1; LA Fischer1; A Ziegler1;

S Ziegler1; S Rieken1; S Bendrich1

1Universitätsmedizin Göttingen, Klinik für Strahlentherapie und

Radioonkologie, Robert-Koch-Straße 4037075 Göttingen

Background: Chemoradiotherapy (CRTx) is an integral part of the mul-

timodal treatment of patients with cervical carcinoma. However, done

postoperatively it leads to signicant toxicity due to high dose exposure

of bladder and bowel. In the context of a clinical series we investigated

the dose-reduced neoadjuvant CRTx in 40 patients with high-risk cervical

carcinoma at the University Hospital of Göttingen.

Methods: 40 patients (mean age 49 yrs, range: 26-74) with high-risk

cervical cancer were treated preoperatively between 2005 and 2018.

Normofractionated RT was delivered over 5 weeks with mean doses of

45 Gy in combination with cisplatin weekly. Patients underwent surgery

within 4-6 weeks aer their last radiotherapy. Data collection was per-

formed using hospital-owned soware (SAP, Aria, iXserv, and Onkostar),

and statistical analysis was performed using Statistika (ethical approval

33/6/21).

Results: Out of 40 patients, 39 underwent surgery and therefore 98% of

the patients were treated per protocol, taking into account good compati-

bility and high compliance. Clinically relevant downstaging was achieved

in 90% of patients. One patient died 5 months aer surgery, the patient

who refused surgery died 74 months aer last RT without any further

therapy. Overall survival rates aer 1, 5 and 10 years were 93, 86 and 70%,

respectively.

Discussion: Dose-reduced neoadjuvant CRTx leads to high response

rates and does not impede surgery. High survival rates were achieved with

moderate acute toxicities, such as low grade cystitis and enterocolitis.

Conclusion: We here present an innovative neoadjuvant treatment

approach for patients with borderline resectable cervical cancer, in whom

impressive rates of response to preoperative CRTx at modest rates of

perioperative and long term toxicities were observed.

Disclosure Statement: e authors declare no conict of interest.

Outcome and toxicity of image-guided boost irradiation in

patients with relapsed prostate cancer after surgery

Fabian Schunn1; Stephan Mende1; Ingmar Schlampp1; Jonas Ristau1;

Anna Kraemer1; Tanja Eichkorn1; Andreas Kudak1; Tim Holland-Letz2;

Klaus Herfarth1; Jürgen Peter Debus1; Stefan A. Koerber1

1Universitätsklinikum Heidelberg, Radioonkologie und Strahlentherapie,

Heidelberg, Deutschland

2Deutsches Krebsforschungszentrum, Heidelberg, Deutschland

Background: Salvage-radiotherapy (SRT) is a common treatment option

in prostate cancer patients with biochemical failure aer primary pros-

tatectomy. It can be performed with simultaneously integrated boost

(SIB) to PSMA-PET-positive lesion, if respective imaging is available at

the time of planning. However, the signicance of SIB during SRT is not

well understood. is study aimed to describe adverse eects (AE) under

SIB-SRT and compared biochemical progression-free survival (bPFS) and

overall survival (OS) between SIB-SRT and regular SRT.

Methods: We reviewed radiation data of patients with biochemical

relapse aer initial prostatectomy, treated with SRT +/- SIB at Heidelberg

University Hospital from 01/2005 to 07/2019. We compared rates of bPFS

and OS as primary endpoints, utilizing the cox model. Secondary end-

point was the descriptive analysis of AE before, under and aer SIB-RT,

following CTCAE version 4 criteria.

Results: A total of 85 patients (23 SIB-SRT, 62 SRT) were eligible for anal-

ysis, median follow-up was 21 months. Patients mostly ranked high-risk

following D’Amico scoring (77,1%, n=64). SIB-SRT showed hazard ratios

of 0.43 (CI: 0,09 – 2,18) for bPFS and 0.08 (CI: 0,03 – 1,83) for OS, p-val-

ues were not signicant. During SIB-SRT no grade IV and only one grade

III AE (urinary congestion) were observed. All patients reported °I-II AE,

most commonly nycturia and diarrhea.

Discussion: A benecial eect of SIB on bPFS and especially OS can

be assumed, however, results were not statistically signicant. SIB-SRT

showed low AE in most patients with improvement 6-8 weeks aer treat-

ment. Limitations of this study are its retrospective approach and small

sample size.

Conclusion: We conclude that SIB-SRT is safe with occurrence of mostly

low grade genitourinary and gastrointestinal AE. Rates of bPFS and OS

were higher in patients with SIB to PSMA-PET-positive lesions, however a

signicant eect could not be demonstrated. A prospective approach and

greater sample size could help to evaluate the signicance of SIB during

SRT.

Disclosure Statement: e authors declare no conict of interest.

191

Oncologic therapy support via means of a dedicated mobile

app – a prospective feasibility evaluation (OPTIMISE-1)

Fabian Schunn1; Rami El Shae2; Andreas Kudak1; Dorothea Kronsteiner1;

Nina Bougatf1; Anna Krämer1; Sebastian Regnery1; Timo Machmer3;

Jürgen Peter Debus1; Nils Henrik Nicolay4

1Universitätsklinikum Heidelberg, Radioonkologie und Strahlentherapie,

Heidelberg, Deutschland

2Universitätsmedizin Göttingen, Strahlentherapie und Radioonkologie,

Göttingen, Deutschland

3Karlsruher Institut für Technologie, Karlsruhe, Deutschland

4Universitätsklinikum Freiburg, Freiburg im Breisgau, Deutschland

Background: Mobile health (m-health) is gaining interest, with mobile

devices being ever more available among medical facilities and patients.

We aimed to examine the feasibility of app-based treatment surveillance

in patients undergoing radiotherapy (RT). Next to technical practicability

and acceptance, we assessed patient satisfaction and quality of life under

treatment.

Methods: is prospective single-center study was performed at

Heidelberg University Hospital between 08/18 - 01/20. During RT we

measured patients’ quality of life (QoL), symptoms and treatment satis-

faction. Respective questionnaires (EORTC QLQ-C30 + diagnose spe-

cic modules, RAND PSQ-18) were presented to patients via a mobile

app, running on a designated tablet device. e primary endpoint was

determined by the fraction of patients, who completed at least 80% of

items. Secondary endpoints were disease-related quality of life and patient

satisfaction.

Result: 49 cancer patients (14 breast, 13 pelvic, 12 bronchial, 10 prostate)

were eligible for analysis. 79,6% [95%-CI: 66.4-88.5%] (n=39) completed

at least 80% of items received by mobile app. A mean of 227,5 +/- 48,25

questions were answered per patient. Breast cancer patients showed the

highest rate of answered questions, with 92,9% (n=13) completing at least

80% of items. QoL and patient satisfaction are reported visually.

Discussion: Patients showed high acceptance with 79,6% (n=39) com-

pleting at least 80% of the given items. Strengths of this study are the pro-

spective approach with a designated app as well as the usage of validated

measurement tools. Limitations are the single-center design and sample

size.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts222

Conclusion: e use of a mobile app for reporting symptoms and QoL

under RT is feasible and well accepted by patients. It may allow for

resource-ecient, detailed feedback to the medical sta and assist in the

assessment of side eects over time. Further interest lies in the develop-

ment of new measurement tools, specically designed for this task.

Disclosure Statement: e authors declare no conict of interest.

227

Radiochemotherapy for locally advanced non-small cell

lung cancer (NSCLC) in patients staged with PET/CT scan vs.

conventional staging: A comparison of treatment patterns,

treatment compliance, and outcomes

Julian Muster; Felix-Nikolai Oschinka Jegor Habermann;

Alexander Ziegler; Sonia Ziegler; Laura Anna Fischer; Andrea Hille;

NiklasJosua Alt; Stephanie Bendrich; Sandra Donath;

Markus Anton Schirmer; Manuel Guhlich; Rami El Shae;

Stefan Rieken; Martin Leu; Leif Hendrik Dröge

University Medical Center Göttingen, Department of Radiotherapy and

Radiation Oncology, Göttingen, Deutschland

Background: In the multicenter PET-Plan trial, a PET/CT based target

volume reduction in denitive radiochemotherapy (RCT) for locally

advanced NSCLC was demonstrated to be safe and eective. We compared

results aer treatment based on PET/CT scan vs. conventional staging.

Methods: A total of 273 patients were included. We compared baseline

and radiotherapy characteristics, treatment compliance, and survival

(Cox regression analysis) between patients who received a PET/CT scan

before treatment (n=170, 62.2%) and patients who underwent conven-

tional staging (n=103, 37.8%).

Result: Patients with PET/CT scan had lower T stages (T1-2, 35.8% vs.

22.3% for conventional staging, p=0.02). Moreover, patients presented

with PET/scan more frequently in the period from 12/2013 to 12/2019

(n=120/137 (87.6%) vs. n=50/136 (36.8%) in the period from 01/2008

to 11/2013, p<0.01). Patients with PET/CT scan received ≥80% of the

planned radiotherapy dose more oen (93.5% vs. 82.5% of the patients

with conventional staging, p<0.01). In multivariable analysis, staging with

PET/CT scan (HR=0.61), age <65 years (HR=0.67), and Karnofsky index

≥90% (HR=0.67) were associated with better overall survival (p<0.05).

Discussion: e lower T stages in patients with PET/CT scan possibly

reect that, when compared to conventional staging, patients with T3-4

tumors were less frequently referred to RCT due to the detection of distant

metastases. PET/CT scan improved the compliance with RT and was asso-

ciated with better patient survival in a similar way like basic parameters

(age, Karnofsky index).

Conclusion: e increasing number of patients with PET/CT scan in the

recent period reects that PET/CT scans were already integrated into clin-

ical practice to a relevant extent. Our results highlight the utmost impor-

tance of PET/CT scans for an adequate patient selection and an eective

treatment in the context of curative RCT. As stated by the investigators of

the PET-Plan trial, a PET/CT scan before RCT should be standard of care.

Disclosure Statement: e authors declare no conict of interest.

234

Postoperative radiotherapy or sequential radiochemotherapy

in the curative treatment of women with uterine sarcoma

Eva Meixner1,2,3; Laila König1,2,3; Andreas Kudak1; Kristin Lang1,2,3;

Jürgen Peter Debus1,2,3,4 5; Juliane Hörner-Rieber1,2,3

1Abteilung für RadioOnkologie und Strahlentherapie, Universitätsklinikum

Heidelberg, Heidelberg, Deutschland

2Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland

3National Center for Tumor diseases (NCT), Heidelberg, Deutschland

4German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation

Oncology, Heidelberg, Deutschland

5Heidelberg Ion Therapy Center (HIT), Heidelberg, Deutschland

Background: Women with uterine sarcoma represent a rare heteroge-

nous group with low unproven evidence regarding the optimal adjuvant

treatment. e aim was to evaluate outcome, toxicity and the impact

of prognostic factors for postoperative radiotherapy (RT) or sequential

radiochemotherapy (RCHT) aer hysterectomy.

Methods: We retrospectively identied 51 patients at the Department of

Radiation Oncology at the University Hospital of Heidelberg, treated with

adjuvant RT or RCHT for carcinosarcomas (CS, n=30), leiomyosarcoma

(LMS, n=14) and endometrial stromal sarcoma (ESS, n=7) between 2001-

2021. All patients were treated with external beam pelvic RT (median

EQD2: 64.4Gy, range: 43.2-80.4Gy), a vaginal surface brachytherapy boost

was added in 40 patients (median boost dose: 10Gy, range: 5-20Gy)

Results: With a median follow-up of 34.7 months, overall survival (OS)

was 89.9%, 73.3% and 51.7% and distant progression free-survival (dPFS)

was 84.0%, 72.3% and 60.7% for 1-, 2- and 5-years, respectively. Local

control (LC) rates for 1- and 5-years were 93.7% and 88.2%. In univariate

Cox analysis, LC was inferior with a higher FIGO stage (p=0.038), posi-

tive resection margins (p=0.013) and serosal involvement (p=0.042) and

interestingly, OS was superior with a shorter time interval from surgery

to start of RT (p=0.047). Multivariate Cox analysis identied higher age

(p=0.044), positive resection margin (p=0.041) and cervical inltration

(p=0.002) as independent prognostic factors for inferior OS. Only moder-

ate toxicity was observed with no high-grade toxicity (CTCAE grade ≥ 4).

Discussion: During the period under review, aliation for CS has

changed towards endometrial carcinoma. Nonetheless, CS, LMS and ESS

suered from extremly poor prognosis, with the vast majority due to dis-

tant failures.

Conclusion: is study conrms the poor OS of women with uterine

sarcoma with high failures in distant control. Radiotherapy shortly aer

hysterectomy appears to be safe and well tolerated achieving ecient

promising LC for this aggresssive, high-risk tumor entity.

Disclosure Statement: e authors declare no conict of interest.

244

Dosimetric comparison of combined pulmonary Stereotactic

Radiotherapy (SBRT) and mediastinal conventionally

fractionated Volumetric Arc Therapy (VMAT) versus

conventionally fractionated VMAT only in advanced stage

Non-Small Cell Lung Cancer (NSCLC)

Tanja Eichkorn1; Cedric Stüwe1; Eric Tonndorf-Martini1; Kai Schubert1;

Sebastian Regnery1; Thomas Held1; Farastuk Bozorgmehr2;

Petros Christopoulos2; Laila König1; Patrick Naumann1;

Sebastian Adeberg1; Klaus Herfarth1; Michael Thomas2; Stefan Rieken3;

Jürgen Peter Debus1; Rami El Shae3

1Department of Radiation Oncology, Heidelberg University Hospital,

Heidelberg, Deutschland

2Thoracic Clinic, Heidelberg University Hospital, Heidelberg, Deutschland

3Department of Radiation Oncology, Göttingen University Hospital, Göttingen,

Deutschland

Background: In radiotherapy planning of inoperable advanced stage

Non-Small Cell Lung Cancer (NSCLC), dose to the lungs can be a limit-

ing factor, especially in case of a peripherally located primary. erefore,

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 223

we evaluated whether normofractionated irradiation of the mediasti-

nal lymph nodes (MLN) combined with stereotactic body radiotherapy

(SBRT) for the primary can achieve a more favorable dose distribution in

the surrounding lung tissue, compared to conventionally fractionated RT

of MLN and primary as a combined target volume.

Methods: Comparative radiotherapy plans were calculated for 21 patients

with inoperable advanced stage NSCLC, extensive metastatic MLN and a

peripherally located primary, as described above. Volumetric modulated

arc therapy (VMAT) technique was used for both SBRT and convention-

ally fractionated RT.

Result: Target volume was smaller with the combined conventional

RT and SBRT approach than with the conventional RT only approach

(median volume [ml]: 307 vs. 441, p=0.0001). Also, low-dose lung expo-

sure (median V5Gy [%]: 71.2 vs. 77.0, p=0.00002) and low-dose heart

exposure (median V5Gy [%]: 40.6 vs. 48.9, p=0.0006) were signicantly

reduced with the combined conventional RT and SBRT approach. ere

was no dierence observed in dose exposure of esophagus and spinal cord.

In this selected cohort, conventional irradiation of primary and MLN in a

single target volume resulted in clinically unacceptable dose exposure of

the lungs necessitating dose reductions or unacceptably impaired target

volume coverage. Clinical data on toxicity and tumor control follow.

Discussion: Irradiated lung volume and dose exposure of organs at risk

was signicantly lower with this tissue-sparing than the conventional

radiotherapy approach.

Conclusion: In cases with peripherally located primary, the combination

of SBRT for the primary and fractionated RT for MLN is dosimetrically

feasible and can provide an alternative to dose reductions necessitated by

otherwise very large target volumes.

Disclosure Statement: e authors declare no conict of interest.

557

Extent of resection margin for oral cavity squamous cell

carcinoma undergoing postoperative radiotherapy: what is an

adequate margin?

Kristin Lang

Universitätsklinik Heidelberg, Radioonkologie, Heidelberg, Deutschland

Background: When adequate resection in patients with oral cavity

squamous cell carcinoma (OCSCC) is attained, no adjuvant treatment

is needed; however, re-resection or radiotherapy may be indicated for

patients with positive margins or in case of extracapsular extension of

lymph nodes. e aim of this study was to examine the clinical signi-

cance and impact of surgical margins size in patients with OCSCC under-

going adjuvant radiotherapy.

Methods: We included 162 patients with OCSCC in this retrospective

study, who underwent postoperative radiotherapy between 2000 and 2019

at the Department of Radiation Oncology, University Hospital Heidelberg

and the German Cancer Research Center. e primary endpoint was

local-control depending on dierent resection margins. Other endpoints

were overall survival (OS), progression-free survival (PFS) and treat-

ment-related toxicity (CTCAE 4.03).

Results: Of 162 patients with OCSCC 77 patients (47.5%) had involved

(<1mm) margins, 22 patients (13.6%) close (1-5mm) margins, and 63

patients (38.9%) clear (>5mm) margins. In multivariate analysis surgical

margin < 5mm was a signicant predictor for worse local control (HR

2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2,

0.7, 2.0).

Conclusions: Especially patients with OCSCC and close margins

(1-5mm) are associated with poor local control rates and early recurrence

and benet from adjuvant radiotherapy. Further prospective studies are

needed to analyze, if a more narrow margin window could be achieved to

better determine appropriate indication of adjuvant radiation treatment.

Disclosure Statement: e authors declare no conict of interest.

573

Quality of teaching radiation oncology in times of

COVID-19 – an analysis of challenges and opportunities

Michael Oertel1; Jan C Becker2; Hans Theodor Eich1

1Klinik für Strahlentherapie - Radioonkologie, Universitätsklinikum Münster,

Münster, Deutschland

2Institut für Ausbildung und Studienangelegenheiten, WWU Münster, Münster,

Deutschland

Background: e COVID-pandemic has challenged medical education

on multiple levels. Radiation Oncology (RO) is a pivotal clinical disci-

pline for the understanding of modern oncology concepts [1]. e follow-

ing analysis aims at providing an overview of students’ evaluation of RO

teaching in the pre- and pandemic situation.

Methods: RO curriculum at our faculty is organized longitudinally span-

ning all clinical semesters which are analyzed here. Students’ evaluation is

mandatory and done on a 101-item Likert scale (0-100; with 0 being the

best grade). Starting from summer semester 2020 onward, lectures were

digitalized and digital implementation was rated on a 11-item Likert scale

(-5-+5; with -5 being the best grade). Evaluation results and participant

numbers between winter semester 2018/2019 and summer semester 2021

were assessed, the rst three semesters being classied as “pre-pandemic”

and the later three as “pandemic”.

Result: Lectures were rated with a median 18.5-21.5 for the 2nd-6th clinical

semester. Comparison between pre-pandemic and pandemic semesters

revealed a deterioration of 1-3 points. Median participants numbers were

63.5-89 with an increase of 12-20 in the pandemic semesters except for

the 6th clinical semester. e percentage of students attending 75 % of RO

lectures in one semester increased considerably (median: 41.4 % vs. 75.3

%). Digital implementation was rated with a median score of -2 to 0.

Discussion: Dierences between pre-pandemic and pandemic evalua-

tions are consistent but small and are unlikely a sign of students’ discon-

tent. Digital formats could augment the numbers of participants as well as

the percentage of presence. Digital implementation was evaluated to be

average to good.

Conclusion: Digital transfer of RO is feasible and good evaluation results

are maintained. Additional concepts with a web-based learning platform

and videocasts are currently being developed.

Indication of source:

1. Oertel M et al (2020) https://doi.org/10.1007/s00066-020-01623-x

Disclosure Statement: e authors declare no conict of interest.

578

Personalized ablative treatment of lymphatic oligometastases

in the abdomen and pelvis: The SMART way

Sebastian Regnery; Carolin Buchele; Lars Piskorski; Fabian Weykamp;

Thomas Held; Tanja Eichkorn; Philipp Hoegen; Carolin Rippke;

C.Katharina Renkamp; Sebastian Klüter; Jonas Ristau; Laila König;

Sebastian Adeberg; Jürgen Peter Debus; Juliane Hörner-Rieber

RadioOnkologie und Strahlentherapie, Universitätsklinikum Heidelberg,

Heidelberg, Deutschland

Background: Oligometastatic disease requires local ablation of all malig-

nant lesions [1]. Oligometastatic spread into abdominopelvic lymph

nodes is a common scenario, particularly in prostate cancer, where pro-

spective evidence supports the benecial use of stereotactic body radio-

therapy (SBRT) [1, 2]. However, SBRT in this region can be challenging

due to the presence of sensitive organs-at-risk (OAR) and frequent prior

irradiations. Stereotactic magnetic resonance (MR)-guided online adap-

tive RT (SMART) is an innovative, personalized approach to SBRT.

Methods: 26 patients received SMART to a total of 31 oligoprogressive

lymph nodes in the abdomen and pelvis from April 2020 – April 2021

inside prospective databases. SMART was delivered on a 0.35 Tesla

MR-linac (MRIdian®, ViewRay Inc.) with calculation of the initial treat-

ment plan on the anatomy of the day (= predicted plan) and possible con-

secutive plan adaptation.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts224

Result: Most patients had prostate cancer (69 %) and most had under-

gone prior irradiations of the abdomen or pelvis (63 %). Aer a median

follow-up of 6.7 months, only one local recurrence and no case of grade ≥

3 toxicity was observed (grade 1/2 toxicity: 39 %). Comparison of 140 pre-

dicted and adapted plans revealed that daily plan adaptation signicantly

reduced inadequate planning target volume (PTV) coverage (predicted:

94%, adapted: 25%) as well as overdoses inside OAR (predicted: 19%,

adapted: 1%) and the PTV (predicted: 15%, adapted: 1%) (all p < 0.001).

Discussion: SMART allows personalized ablative irradiation with prom-

ising clinical and dosimetry results. Particularly, sensitive OAR can be

eectively protected while pursuing high PTV coverage even in challeng-

ing cases, such as re-irradiations.

Conclusion: SMART enables individualized application of ablative doses

and thus safe and eective treatment despite challenging anatomy and/or

prior irradiations.

Indication of source:

[1] Palma DA, et al. (2020). doi:10.1200/jco.20.00818

[2] Ost P, et al. (2018). doi:10.1200/jco.2017.75.4853

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

713

Monocentric comparison of denitive radio(chemo)therapy

[R(C)T] for esophageal cancer in younger (<70 years) versus

older (≥70 years) patients (pat)

Katja Döring; Sonia Ziegler; Jacqueline Possiel; Manuel Guhlich;

MarkusAnton Schirmer; Stefan Rieken; Leif Hendrik Dröge; Martin Leu

Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,

Göttingen, Deutschland

Background: Denitive radio(chemo)therapy [R(C)T] plays a key role in

the treatment of locally advanced inoperable esophageal cancer (LAIEC).

To date, hardly any prospective studies have been established investigat-

ing the therapy of older pat. (≥70 years), so that this retrospective study

compared therapy outcomes, toxicity and compliance between these two

pat. groups.

Methods: 151 pat. ≥18 years without distant metastasis who received

were evaluated. Pat. and tumor characteristics, comorbidities as well as

acute and late toxicities were analyzed. e dierences between the two

groups were compared using Chi² and Mann-Whitney-U test. e pri-

mary endpoints were 5-year overall (OS) and progression-free survival

(PFS), local (LC) and distant (DC) control. Survival analysis was per-

formed by Kaplan-Meier estimator and compared using log-rank test.

Result: 72 pat. were ≥ 70 years and 79 pat. <70 years. Median follow-up

was 12.0 months (2.0-153.0). A median of 60.0 Gy (50.0 Gy - 68.4 Gy) was

applied. Patients received intensity-modulated (n=44) or 3D-conventional

radiotherapy (n=107). Brachytherapy was applied in 47 pat. 126 pat.

received concomitant chemotherapy (CTX). Pat. ≥70 years received as

many CTX treatments as younger pat. Older pat. had more comorbidities

(p<0.01). OS (22.8% vs 16.9%, p=0.31) and PFS (15.7% vs 12.9%, p=0.52)

did not signicantly dier between pat. ≥ 70 years and pat. <70 yrs. LC

(41.8% vs 53.9%, p=0.71) and DC (86.2% vs 90.0%, p=0.32) were similar

between the two groups. Acute and late toxicities did not dier signi-

cantly between the two groups.

Discussion: is retrospective study shows comparable outcome and

toxicity between younger and older pat. treated with RCT for LAIEC.

However, therapy should be strictly indicated by experienced radia-

tion oncologists with respect to comorbidities that are usually present.

Conclusion: Denitive R(C)T is a good treatment option for LAIEC, pro-

viding overall comparable LC and DC between older and younger pat.

with acceptable toxicity.

Disclosure Statement: e authors declare no conict of interest.

747

Symptom relief and oncological outcome in patients

receiving emergency radiation therapy for superior vena cava

syndrome: a single center retrospective analysis of 21 years’

practice

Teresa Esther Maag1; Leif Hendrik Dröge1; Martin Leu1; Sandra Donath1;

Felix-Nikolai Oschinka Jegor Habermann1; Markus Anton Schirmer1;

Laura Anna Fischer1; David Alexander Ziegler1; Rami El Shae1;

Stefan Rieken1; Manuel Guhlich1

1Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie und

Radioonkologie, Göttingen, Deutschland

Background: Superior vena cava syndrome (SVCS) is a group of symp-

toms caused by obstruction of the superior vena cava. Leading symptoms

are shortness of breath and swelling of neck and face. SVCS can lead to

several life-threatening consequences, e.g. brain edema. Mainly caused by

malignant tumor growth, progressed SVCS oen presents as a medical

emergency. erapies include glucocorticoids, chemotherapy, endovascu-

lar stenting and urgent radiotherapy (RT).

Methods: To evaluate treatment outcomes, we examined patients receiving

RT for SVCS in the Department of Radiation erapy and Radiooncology,

University Medical Center in Göttingen, in the years 2000 – 2020. Local

ethics committee approval was obtained, data was retrieved from the

patients’ medical records. Primary endpoint was symptom relief; second-

ary endpoints were oncological outcome and treatment-related toxicity.

Result: 132 patients were screened, 83 patients were eligible for analysis.

Main diagnosis was bronchial carcinoma (65 patients; 78,3%). 25 patients

(30,1%) did not nish RT; 16 patients (19,3%) died during therapy, three

of which received only one or two RT fractions.

Clinical symptom relief was achieved In 43 patients (65,2%), 23 patients

(34,8%) did not benet clinically. In 17 patients, no data was available.

40 patients (48,2%) showed any RT related side eects, 25 patients (30,1%)

at least toxicity grade 2 as scored by Common Toxicity Criteria, V5.0.

Primary toxicity was dysphagia (total 27 patients, 32,5%, ≥ grade 2: eight

patients, 9,6%).

Patients’ mean overall survival was 104,7 days (range: 2-929). 18 Patients

were lost to follow up. ree patients were still alive at last follow-up

(08/2021).

Discussion: Our data show a clinical symptom relief for 65% of patients

suering from SVCS. Outcomes may be biased due to individual physi-

cians’ assessment, causing primary tumor and concomitant therapies.

Conclusion: RT for SVCS is a feasible and oen benecial emergency

procedure with acceptable acute side eects. Even though it oen occurs

in advanced cancer, long-term survival can be achieved.

Disclosure Statement: e authors declare no conict of interest.

757

Symptom relief and oncological outcome in patients receiving

emergency radiation therapy for acute tumor associated

hemoglobin relevant bleedings: a single center retrospective

analysis of 21 years´ practice

Teresa Esther Maag1; Andrea Hille1; Rami El Shae1; Sandra Donath1;

Stephanie Bendrich1; Friedemann Nauck2; Martin Leu1;

Leif Hendrik Dröge1; Laura Anna Fischer2; Markus Anton Schirmer1;

Stefan Rieken1; Manuel Guhlich1

1Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie und

Radioonkologie, Göttingen, Deutschland

2Universitätsmedizin Göttingen, Klinik für Palliativmedizin, Göttingen,

Deutschland

Background: Acute tumor associated hemoglobin relevant bleeding

(ATAHRB) is a rather frequent and feared complication in oncology.

Depending on the localisation of the haemorrhage, established therapies

include compression, sclerotherapy, radiological intervention and urgent

radiotherapy (RT).

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 225

Methods: To evaluate treatment outcomes in emergency RT for ATAHRB,

we examined patients treated in the Department of Radiation erapy

and Radiooncology, University Medical Center in Göttingen, Germany,

in the years 2000 – 2020. Local ethics committee approval was obtained,

data was retrieved from the patients’ medical records. Primary Endpoint

was bleeding stop; secondary endpoints were oncological outcome and

treatment-related toxicity.

Result: 101 patients were screened. A total of 84 patients were eligible

for analysis. 33 patients (39,3%) were treated for gynaecological carci-

noma, 19 patients (22,6%) for urological carcinoma, eight patients (9,5%)

for gastrointestinal carcinoma, seven patients (8,3%) for lung cancer; 17

patients (20,2%) for other tumors.

In 75 patients (89,3%), a bleeding stop was reported clinically. Eight

patients (9,5%) did not benet, in one patient (1,2%), no data was avail-

able. 14 patients (16,7%) did not nish the treatment, ve patients (6%)

died during therapy.

41 patients (48,8%) showed any radiation related side eects, 18 patients

(21,4%) at least toxicity grade 2 as scored by Common Toxicity Criteria,

V5.0. Most patients (n=32, 38,1%) suered from gastrointestinal and/or

genitourinary side eects, 8 patients (9,5%) at least grade 2.

Mean overall survival (OS) was 344,2 days (range: 3-5455). 31 patients

were lost to follow up. One patient was still alive at last follow-up (08/2021).

Discussion: Consistent with previously published data, our results show

a highly eective therapy for ATAHRB. Remarkably, mean OS in this pri-

marily palliative patient cohort was 344 days.

Conclusion: RT for ATAHRB proved to be a safe and very eective emer-

gency procedure with acceptable acute side eects.

Disclosure Statement: e authors declare no conict of interest.

783

Irradiation of the source cells impacts the eects of secreted

exosomes in target cells

Mahtab Lashgari1; Bettina Priesch-Grzeszkowiak1; Anja Grillenberger1;

Pascaline Kouam-Daniel1; Jan P. Boström2; Irenäus A. Adamietz1; Helmut

Bühler1

1Klinik für Strahlentherapie und Radio-Onkologie, Universitätsklinikum Marien

Hospital, Herne, Deutschland

2Gamma Knife Zentrum, Knappschaftskrankenhaus Bochum, Bochum,

Deutschland

Background: We investigated whether exosomes from glioblastoma cells

aect malignancy when taken up by cells of the same lineage and whether

dierences exist when the secreting cells were previously irradiated.

Methods: e malignancy parameters motility, invasiveness, prolifera-

tion, and clonogenic survival were examined by videography, 3d matrix

degradation, colorimetric viability assay, and colony formation.

Result: Both exosome fractions signicantly aected the parameters

studied with signicant dierences between the two fractions. Overall, it

appeared that exosomes from unirradiated cells signicantly increased the

malignancy of target cells, while exosomes from irradiated cells tended to

reduce it.

Discussion: Malignant cells appear to communicate materially via exo-

somes and pass on the information "irradiated" in this way.

Conclusion: It is possible that this is a mechanism that contributes to

bystander and abscopal eects.

Disclosure Statement: e authors declare no conict of interest.

Rehabilitation and long-term burden in social medicine (survivor)

Best-of-Abstract-Vortrag

Treatment decision regret in long-term prostate cancer

survivors after radical prostatectomy: a longitudinal study

Valentin H. Meissner1; Barbara W. Simson1; Andreas Dinkel2; Stefan

Schiele1; Donna Ankerst3; Jürgen Gschwend1; Kathleen Herkommer1

1Technische Universität München, Klinik und Poliklinik für Urologie,

Universitätsklinikum rechts der Isar, München, Deutschland

2Technische Universität München, Klinik und Poliklinik für Psychosomatische

Medizin und Psychotherapie, Universitätsklinikum rechts der Isar, München,

Deutschland

3Technische Universität München, Lehrstuhl für Mathematische Modelle

biologischer Systeme, Fakultät für Mathematik, Garching, Deutschland

Background: Patients diagnosed with localized prostate cancer (PC) have

to choose between several treatment options. Treatment complications

and poor oncologic outcomes can lead patients to regret their initial treat-

ment choice.

Methods: 1,003 survivors from the multicenter German Familial PC data-

base submitted questionnaires on treatment decision regret in 2007 (T1)

on average 7 years aer radical prostatectomy and then again 13 years

later in 2020 (T2). Patients completed standardized patient-reported

outcome measures on decision-making, quality of life, and psychosocial

factors. Hierarchical multivariable logistic regression was used to assess

predictors of longitudinal decision regret.

Result: Decision regret increased signicantly over time (9.0% aer 6.9

years in 2007 and 12.1% aer 19.9 years in 2020; p=0.009). Patients with

stable decision regret at both time points reported signicantly more

oen a passive decision-making role compared to patients with stable no

decision regret (27.8% vs. 10.6%; p=0.005). Patients with stable no deci-

sion regret had higher scores in quality of life compared to patients with

stable and increasing decision regret, respectively (0.69 vs. 0.65 and 0.62,

respectively; p=0.013). Organ-conned disease (OR 1.82, 95% CI 1.03-

3.21), decision regret in 2007 (OR: 6.40, 95% CI 3.56-11.51), and a higher

depression score (OR 1.42 95% CI 1.07-1.89) were associated with deci-

sion regret in 2020. Shared decision-making (OR: 0.55 95% CI 0.32-0.92)

was associated with less decision regret.

Discussion: A profound understanding of determinants of decision regret

may optimize the initial treatment decision making process leading to

lower decision regret and quality of life improvements in PC survivors.

Conclusion: Findings of the present study underline the perseverance

of decision regret in long-term PC survivors and the denitive need for

involving patients in the decision-making process to mitigate regret over

the long term.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts226

Poster

Health and Nutritional Status after radical prostatectomy

Marc Heydenreich1; Alexander Stäuber2; Dirk-Henrik Zermann1

1Vogtland-Klinik Bad Elster, Bad Elster, Deutschland

2Chemnitz University of Technology, Professorship of Sports Medicine / Sports

Biology, Chemnitz, Deutschland

Background: e Bioelectrical Impedance Analysis (BIA) enables an

assessment of the body compartments and the phase angle is used to

assess the course of the disease (1, 2). e aim of the study was, what

inuence does the stress associated with diagnostics and therapy have on

the phase angle aer radical prostatectomy.

Methods: A total of 103 patients aer radical prostatectomy were exam-

ined using BIA.

Result: 40–55-year-old patients (n=8): BMI= 28.2; phase angle 5.6 (0.3);

reference value 6.5 (0.2)

56-70-year-old patients (n=62): BMI= 27.9; phase angle 5.2 (0.6); refer-

ence value 6.0 (0.2)

71-85--year-old patients (n=33): BMI= 26.4; phase angle 4.7 (0.8); refer-

ence value 5.3 (0.2)

Discussion: e results show that a lower phase angle is measured with

increasing age. As a result, older prostate cancer patients have a poorer

nutritional or health status.

In comparison to the age-specic normal value, the phase angle in patients

aer radical prostatectomy is signicantly lower (Bosy-Westphal 2006).

Conclusion: According to current scientic knowledge, the phase angle

allows conclusions about nutritional-, hydration-, functional status and the

morbidity and mortality risk of the patient (Stobäus 2010). Consequently,

the tasks of rehabilitation and aercare is restoring an adequate training

and nutritional status aer completing primary cancer therapy. In addi-

tion to targeted physiotherapeutic and sports science treatments, this also

requires nutritional medical interventions.

Indication of source:

1. Bosy‐Westphal A, Danielzik S, Dörhöfer RP, Later W, Wiese S, Müller MJ.

Phase angle from bioelectrical impedance analysis: population reference values

by age, sex, and body mass index. Journal of Parenteral and Enteral Nutrition.

2006;30(4):309-16.

2. Stobäus N, Norman K, Pirlich M. Phasenwinkel und Bioelektrische Impedanz-

vektoranalyse–Klinische Anwendbarkeit der Impedanzparameter. Aktuelle

Ernährungsmedizin. 2010;35(03):124-30.

Disclosure Statement: e authors declare no conict of interest.

Poster

Rehabilitation and long-term burden in social

medicine (survivor)

230

Degree of urinary incontinence after neobladder surgery -

variation in last ten years

Marc Heydenreich; Dirk-Henrik Zermann

Vogtland-Klinik Bad Elster, Bad Elster, Deutschland

Background: Overcoming urinary incontinence aer cystectomy and

forming a neobladder is a particular challenge. e aim of this study was

to evaluate the development of the continence situation aer creation of a

neobladder in the period from 2010 to 2020.

Methods: 621 neobladder patients performed a 24-hour Pad Test at the

beginning of a 3-week-rehabilitation. For the statistical evaluation, an

SQL query of the data from 2010-2020 was carried out and evaluated.

Result:

• year 2010 (n=68): urine loos/ 24h= 587.1g

• year 2011 (n=57): urine loos/ 24h= 617.0g;

• year 2012 (n=51): urine loos/ 24h= 395.3g;

• year 2013 (n=63): urine loos/ 24h= 517.9g;

• year 2014 (n=53): urine loos/ 24h= 573.2g;

• year 2015 (n=58): urine loos/ 24h= 536.5g;

• year 2016 (n=61): urine loos/ 24h= 609.4g;

• year 2017 (n=62): urine loos/ 24h= 567.3g;

• year 2018 (n=66): urine loos/ 24h= 538.1g;

• year 2019 (n=46): urine loos/ 24h= 661.6g;

• year 2020 (n=36): urine loos/ 24h= 434.5g;

Discussion: e postoperative 24-hour urine loss is 552.8 g/ 24h on aver-

age (varying between min. 2 g and max. 3170 g).

Conclusion: e results show that the early postoperative amounts of

urine lost aer neobladder are subject to variation in the period from 2010

to 2020. A trend towards reduction over the last ten years, as in the case

of post-radical prostatectomy, cannot be demonstrated [1]. is is most

likely due to the complex anatomical and physiological changes that result

from the neobladder. is underlines the importance of individual reha-

bilitation treatment and enables timely progress through a combination of

dierent continence and coordination techniques [2].

Indication of source:

1. Heydenreich M, Zermann DH, Historische Entwicklung der Harnverlustmen-

gen nach radikaler Prostatektomie von 2010–2019, Der Urologe; 2020.

2. Heydenreich M, Zermann DH, Harninkontinenz nach Anlage einer

Neoblase– Ezienz eines sensomotorischen Trainings, Der Urologe; 2020.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 227

Poster

Rehabilitation and long-term burden in social

medicine (survivor)

419

Ecacy of a memory and psychomotor intervention in

cancer-related cognitive impairment: design of a randomized

controlled trial

Joschua Mirko Reis1; Anna Ballweg1; Mia Wallis1; Antonia Rabe2;

Ralf C. Bargou3; Elisabeth Jentschke2

1Faculty of Medicine , Julius-Maximilians University of Würzburg, Medical

Student, Würzburg, Deutschland

2Comprehensive Cancer Center Mainfranken, University Hospital Würzburg,

Psychoonkology, Würzburg, Deutschland

3Comprehensive Cancer Center Mainfranken, University Hospital Würzburg,

Würzburg, Deutschland

Background: Cancer patients oen suer from impairments in their

cognitive functionality. An intervention consisting of memory and psy-

chomotor training (MPMT) improved cognition of geriatric patients

(Oswald et al., 2006). A comparable intervention has not been evaluated

in patients with cancer-related cognitive impairment (CRCI) yet. e aim

of the study is to investigate eects of MPMT intervention on cognition

in patients with CRCI.

Methods: Adult patients with dierent types of cancer and treatment

will be recruited at the University Hospital Würzburg. Recruitment

begins in autumn 2021. Study participants will be randomly assigned to

MPMT intervention or waiting group including standard treatment in a

1:1 ratio. MPMT is an 8-week online training made for groups of 8 (1h/

week). Participants complete assessments at baseline, post-intervention,

and 6 months post-intervention. Assessments examine cognitive func-

tion (Test battery for the assessment of attentional functioning (Alertness,

Go-/Nogo, working memory), Verbal Learning and Memory Test, Trail

Making Test, FACT-Cog), physical performance (6-minute-walk test),

quality of life (EORTC-QLQ-30), experienced attention decits (FEDA)

and potential confounders such as anxiety (GAD-7), depression (PHQ-9),

distress (Distress ermometer), comorbidities (e. g. cancer-related

fatigue (EORTC-QLQ-FA12)). e primary outcome is the alertness of

participants in the intervention group compared to those in the control

group. Necessary sample size is 152 subjects (power 80%; p-level <0.05;

R2 = 0.5; drop-out rate of 20%, PASS 2020). Dierences between groups

are determined by using an analysis of covariance.

Discussion: is study is the rst randomized controlled trial that exam-

ines changes in cognitive functions of a MPMT online group intervention

in patients with CRCI. A limitation is that blinding of patients is not possi-

ble due to usual care in the control group and could lead to placebo eects

in the intervention group.

Disclosure Statement: e authors declare no conict of interest.

Poster

Rehabilitation and long-term burden in social

medicine (survivor)

455

Development and evaluation of the website Onko-Vital

for the oncological rehab-aftercare

Heike Kähnert1; Birgit Leibbrand2

1Institut für Rehabilitationsforschung, Norderney, Bad Salzuen, Bad Salzuen,

Deutschland

2Salzetalklinik, Bad Salzuen, Deutschland

Background: In this study we present the development and initial review

of Onko-Vital: an online rehab aercare program. A participatory devel-

opment process is a central aspect of this project to align the Onko-Vital

website with the needs of oncological patients.

Methods: For the development of the website, oncological patients were

asked about the design and content of online rehab aercare programs via

group interviews (n = 4) and questionnaires (n = 130). Both the Onko-

Vital prototype and the associated Onko-Vital training were subjected to

an initial review with oncological patients (n = 50).

Results: According to the participants, an online rehab aercare pro-

gram should provide information, tutorials, and tips on therapy-related

side eects (approval: 83%), nutrition (90%), physical activity (80%), and

mental health (66%). In addition, a forum (42%) and the possibility of

recording their own aercare goals (54%) should be part of the program.

During rehab, training session on website use should be oered (78%).

In addition, the interviews provide insight into the user’s perception on

usability and clarity of the website. During the pilot phase, the participants

received the Onko-Vital training in the second rehab week and were able

to use the website on a smartphone or tablet from the third rehab week.

94% of the participants rated the training as (very) good and 96% as prac-

tical. Furthermore, 94% of the participants felt(very) good prepared on

how to use the Onko-Vital website aer the training concluded. At the end

of the rehab, the website is rated as versatile (86%), professional (86%),

and attractively designed (92%). e handling of Onko-Vital is easy to

understand (78%), aiding the user’s orientation and ability to search for

specic information (72%). 94% of the participants want to use the web-

site at home.

Conclusions: e development of Onko-Vital was successfully completed

through a participatory process. Onko-Vital is accepted by patients and

rated overwhelmingly positive. An RCT-study is currently being carried

out to check the eectiveness of Onko-Vital.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts228

Poster

Rehabilitation and long-term burden in social

medicine (survivor)

851

Return to work, fatigue and cancer rehabilitation after

curative radiotherapy and radiochemotherapy for pelvic

gynecologic cancer

Eva Meixner1,2,3; Ilse Weis4; Daniela Roob4; Elisabetta Sandrini1,2,3;

Line Hoeltgen1,2,3; Tanja Eichkorn1,2,3; Philipp Hoegen1,2,3; Laila König1,2,3;

Nathalie Arians1,2,3; Markus Wallwiener5; Jürgen Peter Debus1,2,3;

Juliane Hörner-Rieber1,2,3

1Abteilung für RadioOnkologie und Strahlentherapie, Universitätsklinikum

Heidelberg, Heidelberg, Deutschland

2Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland

3National Center for Tumor diseases (NCT), Heidelberg, Deutschland

4Social Service Counselling, Heidelberg University Hospital, Heidelberg,

Deutschland

5Department of Gynecology and Obstetrics, Heidelberg University Hospital,

Heidelberg, Deutschland

Background: Pain, fatigue and depression are a common cluster of symp-

toms among cancer patients that impair quality of life and daily activities.

We aim to evaluate the burden of cancer rehabilitation, return to work

(RTW) and a more in-depth understanding of the impacts of treatment

for post-therapy recovery.

Methods: Tumor and treatment characteristics, lifestyle and house-

hold data, the use of in-house social services, post-treatment inpatient

rehabilitation and RTW were assessed for 424 women, diagnosed with cer-

vical, uterine, vaginal and vulvar cancer, receiving curative radio(chemo)

therapy.

Result: RTW rates for progression-free women aer RT at 3 and 6 months

were 32.3% and 51.0%, and increased at 12 and 18 months to 58.1% and

63.2%, respectively. Progressive disease, the presence of fatigue or pain,

salaried employment, depression and a body weight outside normal

ranges were signicantly associated with lower RTW rates. Patients with

higher FIGO stages and intensied treatment signicantly suered from

more acute pain and fatigue. e Charlson Comorbidity Index reliably

predicted patients associated with signicantly higher rates of fatigue.

Aside from the presence of children, no other household/lifestyle factor

was correlated to increased fatigue rates. Women aged ≤45 years had a sig-

nicantly higher risk of developing depression requiring treatment during

follow-up. Post-treatment inpatient cancer rehabilitation, including exer-

cise and nutrition counseling, signicantly relieved fatigue symptoms.

Discussion: Social support services and post-treatment inpatient cancer

rehabilitation programs were helpful in keeping patients connected to

their professional lives. Mental issues and the development of depression

during follow-up remains an issue particularly for younger patients.

Conclusion: e burdens for recovery from cancer therapy remain

multi-factorial. Special focus needs to be placed on identifying high-risk

groups experiencing fatigue or pain. Specialized post-treatment inpatient

cancer rehabilitation can improve RTW rates.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Poster

Rehabilitation and long-term burden in social

medicine (survivor)

997

Quality of life in long-term survivors of pediatric cancer in

comparison with the general population and associations

with health behavior, health risk factors, and physical illness

Mareike Ernst1; Andreas Hinz2; Elmar Brähler1; Jörg Faber3; Philipp S. Wild4;

Hiltrud Merzenich5; Manfred E. Beutel1

1Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,

Deutschland

2Abteilung für Medizinische Psychologie und Medizinische Soziologie,

Universitätsklinikum Leipzig, Leipzig, Deutschland

3Pädiatrische Hämatologie/Onkologie/Hämostaseologie, Universitätsmedizin

der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und

Jugendmedizin, Mainz, Deutschland

4Präventive Kardiologie und Medizinische Prävention, Universitätsmedizin

der Johannes Gutenberg-Universität Mainz, Zentrum für Kardiologie, Mainz,

Deutschland

5Institut für Medizinische Biometrie, Epidemiologie und Informatik,

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,

Deutschland

Background: We aimed to compare the quality of life (QOL) reported by

childhood cancer survivors (CCS) drawn from a cohort of the German

Childhood Cancer Registry with a representative population sample and,

within CCS, to test associations between QOL and health behavior, health

risk factors, and physical illness.

Methods: CCS (N = 633, age at diagnosis M = 6.34 (SD = 4.38), age at

medical assessment M = 34.92 (SD = 5.70)) and a general population sam-

ple (age-aligned; N = 975) lled out the EORTC QLQ-C30. Comparisons

were performed using General linear models (GLMs) (xed eects: gen-

der, group (CCS vs. population); covariates: age, education level). CCS

underwent an extensive medical assessment (mean time from diagnosis

to assessment was 28.07 (SD = 3.21) years) including objective diagno-

sis of health risk factors and physical illnesses (e.g., diabetes and cardio-

vascular disease). Within CCS, we tested associations between QOL and

sociodemographic characteristics, health behavior, health risk factors, and

physical illness.

Result: CCS reported both worse functional QOL and higher symptom

burden than the population. Female CCS reported particularly low QOL

and high symptom burden. Among CCS, better total QOL was related to

younger age, higher level of education, being married, and engaging in

active sports. Both health risk factors and manifest physical illnesses were

associated with lower total QOL.

Discussion: In all domains, long-term CCS reported worse QOL than the

comparison sample.

Conclusion: e negative associations with risk factors and physical

illnesses indicate an urgent need for long-term surveillance and health

promotion.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 229

Sarcoma

Best-of-Abstract-Vortrag

486

A post hoc analysis of the EPAZ trial: the role of geriatric

variables in elderly soft tissue sarcoma (STS) patients on

toxicity and outcome

Rainer Hamacher1,2; Xiaofei Liu3; Markus K. Schuler4; Leopold Hentschel5;

Patrick Schöski6; Hans-Georg Kopp7; Sebastian Bauer1,2; Bernd Kasper8;

Lars Lindner9; Jens Chemnitz10,11; Martina Crysandt12; Alexander Stein13;

Björn Steen14; Stephan Richter5; Gerlinde Egerer15; Philipp Ivanyi16;

Annegret Kunitz17,18; Viktor Grünwald2,19,20

1Department of Medical Oncology, Sarcoma Center, West German Cancer

Center, University Hospital Essen, Essen, Deutschland

2German Cancer Consortium (DKTK), Partner site University Hospital Essen

3Institute for Biostatistics, Medical School Hannover, Hannover, Deutschland

4MVZ Onkologischer Schwerpunkt am OHH, Berlin, Deutschland

5University Hospital Carl Gustav Carus, University Cancer Center/Medical

Department I, Dresden, Deutschland

6Department of General Medical Oncology, University Hospitals Leuven, Leuven

Cancer Institute, KU Leuven, Löwen, Belgien

7Robert Bosch Centrum für Tumorerkrankungen Stuttgart, Stuttgart,

Deutschland

8Sarcoma Unit, Mannheim University Medical Center, Mannheim, Deutschland

9Department of Medicine III, University Hospital, Ludwig Maximilian University

Munich, München, Deutschland

10Community Hospital Middle Rine, Koblenz, Deutschland

11Department of Hematology, Oncology, Clinical Infectious Diseases, Clinical

Immunology, Hemostaseology and Medical Intensive Care, University Hospital

Cologne, Köln, Deutschland

12University Hospital RWTH Aachen, Aachen, Deutschland

13University Hospital Hamburg-Eppendorf, Hamburg, Deutschland

14University Hospital Frankfurt, Frankfurt am Main, Deutschland

15University Hospital Heidelberg, Heidelberg, Deutschland

16Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, ,

Medical School Hannover, Hannover, Deutschland

17Vivantes Clinic Berlin-Spandau, Berlin, Deutschland

18Department of Hematology, Oncology and Tumor Immunology, University

Hospital Charite, Berlin, Deutschland

19Interdisciplinary Genitourinary Oncology at the West German Cancer Center,

Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University

Hospital Essen, Essen, Deutschland

20Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation,

Medical School Hannover, Hannover, Deutschland

Background: e EPAZ study (NCT01861951) recently showed that

pazopanib was non-inferior to doxorubicin in patients ≥ 60 years treated

in rst line for advanced STS [1].

Methods: Patients ≥ 60 years with advanced STS were randomized for

treatment with either pazopanib or doxorubicin. Geriatric assessment [G8

screening tool, Charlson Comorbidity Index (CCI), instrumental activ-

ities of daily living (IADL) and social situation] were assessed at base-

line. Age > 75 years, liposarcoma, ECOG = 2, G8 ≤ 14, IADL ≥ 1 and

CCI ≥ 2 were tested for their impact on progression-free survival (PFS),

overall survival (OS), CTCAE grade 3/4 adverse events (AEs) or serious

AEs (SAEs), using Kaplan-Meier method and Cox proportional hazards

model. Treatment was always included as a covariate in the Cox model.

Result: Univariate analysis showed an increased risk of grade 3/4 AEs and

SAEs for ECOG = 2, G8 score ≤ 14 and IADL ≥ 1, independent of treat-

ment. Multivariate analysis showed for pazopanib a signicant reduced

risk for grade 3/4 AEs (HR 0.53; p = 0.033) and G8 ≤ 14 an increased

risk for SAEs (HR 2.67; p = 0.011). Regarding outcome, on multivari-

ate analysis, G8 ≤ 14 was a negative prognostic factor for PFS (HR 1.82;

p = 0.009) and IADL ≥1 for OS (HR 2.02; p = 0.007). ECOG = 2 was

the strongest negative predictor for PFS (HR 4.39; p = 0.001) and OS

(HR 3.74; p = 0.004). Neither age nor CCI showed any impact on PFS, OS,

grade 3/4 AEs or SAEs.

Discussion: is post hoc analysis demonstrated that age is not a denom-

inator for outcome or toxicity in elderly STS patients. Instead, functional

assessment is of prognostic and predictive value. Moreover, pazopanib has

a reduced risk for grade 3/4 AEs compared to doxorubicin.

Conclusion: Geriatric assessment should be used to counsel patients and

tailor therapy to individual needs.

Indication of source:

1 Grünwald V, Karch A, Schuler M, Schöski P, Kopp HG, Bauer S, et al. Rando-

mized Comparison of Pazopanib and Doxorubicin as First-Line Treatment in

Patients With Metastatic So Tissue Sarcoma Age 60 Years or Older: Results of

a German Intergroup Study. J Clin Oncol. 2020;38(30):3555-64.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Poster

177

High-grade osteosarcoma of bone of elderly patients (65+

years): Results of the cancer registry Baden-Württemberg

Miriam Wilhelm1; Irina Surovtsova2; Marlies Günther-Gunkel3; Philipp

Morakis4

1Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,

Geschäftsstelle Qualitätskonferenzen, Stuttgart, Deutschland

2Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,

Stabsstelle Statistik, Stuttgart, Deutschland

3Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,

Datenmonitoring, Stuttgart, Deutschland

4Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg, Leitung

Geschäftsstelle Qualitätskonferenzen, Stuttgart, Deutschland

Purpose: In these results we report characteristic at diagnosis as well as

treatment of elderly osteosarcoma patients in Baden-Württemberg.

Methods: To present patient´s characteristics (age, gender, histology, site,

primary metastases, pre-existing cancer disease), treatment (systemic-

and radiotherapy, operation) and outcome (vital status) patients (aged

65 +) with high-grade osteosarcoma (ICD-O: 9180/3, 9181/3, 9182/3,

9183/3, 9184/3, 9185/3 or 9186/3) that were reported to the cancer regis-

tration since 2012 were included in these analyses.

Preliminary Results: Data of 32 patients with high-grade osteosarcoma of

bone were registered between 2012 and 2020 (15 males, 17 females), mean

age was 73 years, 39% had primary metastases (unknown 9 patients).

Tumor site: extremity 15, trunk 12 (including 5 pelvis), craniofacial 5. 22

patients received surgery, 8 radiotherapy, 10 chemotherapy, for 11 patients

out of these it was a combination of therapies (no therapy reported 4).

Discussion: Elderly patients are oen excluded in study protocols and

data in non-obligatory registries is incomplete. e data from popula-

tion-based registries however, can provide insights on specic subgroups.

e data presented here are not in line with the results reported by Longhi

et al. (2008; Osteosarcoma in patients older than 65 years. J Clin Oncol.

26(33), 5368-5373) for site and treatment. is may be due to therapy

changes since 2008 as well as to the dierent source and structure of data

collection.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts230

Conclusion: Even though the database of cancer registries has limitations

concerning clinical data when compared to clinical studies or detailed

patient chart information, this population based data is very evaluable,

especially for rare diseases such as osteosarcoma. Due to region-wide

mandatory notication of a standardized dataset, detailed evaluations of

rare cancer diseases are possible.

Disclosure Statement: e authors declare no conict of interest.

219

A novel immune-related gene signature predicting survival in

sarcoma

Haoyu Ren1; Alexandr Bazhin1,2; Elise Pretzsch1; Sven Jacob1; Haochen Yu1;

Jiang Zhu3; Markus Albertsmeier1; Lars Lindner4; Thomas Knösel5;

Jens Werner1,2; Martin Angele1,2; Florian Bösch1,6

1Ludwig-Maximilians-University Munich, Department of General, Visceral, and

Transplant Surgery, Munich, Deutschland

2German Cancer Consortium (DKTK), Partner Site Munich, Munich, Deutschland

3West China Hospital, Sichuan University, Department of Liver Surgery and Liver

Transplantation Centre, Chengdu, China, VR

4University Hospital, LMU Munich, Department of Medicine III, SarKUM, Munich,

Deutschland

5University Hospital, LMU Munich, Institute of Pathology, Munich, Deutschland

6University Medical Center Goettingen, Department of General, Visceral and

Pediatric Surgery, Goettingen, Deutschland

Background: Sarcomas are a heterogeneous group of rare mesenchymal

tumors. e current risk stratication system is insucient to provide

precise survival prediction and treatment response. us, valid prognostic

models are needed to guide treatment.

Methods: is study analyzed the gene expression and outcome of 980 sar-

coma patients from seven public datasets. e abundance of immune cells

and the response to immunotherapy was calculated in the ImmuCellAI

database. Immune-related genes (IRG) were screened through weighted

gene co-expression network analysis (WGCNA). LASSO Cox regression

was used to establish a powerful IRG signature predicting prognosis. We

divided patients into high and low-risk groups based on the risk score of

the IRG signature and compared survival between groups. Moreover, we

developed a nomogram and a decision tree integrating the IRG risk score

and clinicopathological parameters.

Result: e identied IRG signature incorporated 14 genes and identied

high-risk patients in the training and six validation cohorts. Multivariate

survival analyzes revealed that the 14-IRG signature served as an indepen-

dent risk factor for overall and disease-free survival. Moreover, the IRG

signature acted as a potential indicator for immunotherapy. e nomo-

gram based on the IRG signature risk score outperformed presented tra-

ditional clinicopathological features in survival prediction. e decision

tree discriminated risk subgroups powerfully.

Discussion: In the developed 14-IRG signature, TRIM21 and NT5DC2

may be the novel biomarkers and therapeutic target for sarcoma. A nomo-

gram and a decision tree based on the IRG signature act as an accurate and

practical predictive tool identifying high-risk patients with low survival

rates. It also provides an opportunity to identify patients with sarcomas

eligible for immune checkpoint inhibitor therapy.

Conclusion: In summary, the proposed IRG signature is a robust bio-

marker to predict outcome and treatment response in sarcoma patients.

Disclosure Statement: e authors declare no conict of interest.

251

Prophylactic lymphaticovenous anastomoses for resection

ofsoft tissue tumors of the thigh

Johannes Maximilian Wagner; Mehran Dadras; Markus Lehnhardt;

Bjoern Behr

Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil Bochum,

Plastische Chirurgie, Bochum, Deutschland

Purpose: Patients with so tissue tumors of the extremities are at risk

to develop secondary lymphedema aer tumor resection caused by dis-

ruption of lymphatic vessels and sclerosis. Lymphaticovenous anastomo-

sis (LVA) is a minimally invasive procedure capable of creating a bypass

for restoration of lymphatic drainage in early stages of lymphedema. is

study aimed to evaluate the benecial eects of LVAs aer so tissue tumor

resection of the thigh in a prophylactic approach. Methods: In a retro-

spective case control study, we compared 8 patients who received LVAs in

combination with tumor resection for the treatment of so tissue tumors

of the thigh with a prior cohort of 20 patients who received so tissue sar-

coma resection of the thigh. All patients receiving LVA were assessed for

development of lymphedema via bilateral measurements of circumference

and assessment of lymphedema quality of life index (LyQLI). Outcome

data were obtained from the control cohort by assessment of swelling of

the aected limb, need for compression garments and the LyQLI.

Results: Only one of the eight patients who received LVAs showed moder-

ate impairment in the LyQLI at a follow-up of 12 months while 45% of the

control cohort patients complained about symptoms of secondary lymph-

edema at a median follow-up of 22 months. Furthermore, no lymphedema

could be observed in circumferential and ICG measurements in LVA

patients.

Discussion: LVAs performed in combination with tumor resection

of thigh so tissue tumors could eectively reduce the negative conse-

quences of lymph transport disruption and prevent development of sec-

ondary lymphedema.

Conclusion: Although performing LVAs in most patients with so tissue

tumors would be favorable, this procedure should be limited to patients

who are at a high-risk developing lymphedema such as large tumors

located adjacent to dominant lymph paths of the extremities.

Disclosure Statement: e authors declare no conict of interest.

292

Fusion of preoperative in situ magnetic resonance imaging

and postoperative computed tomography of the specimen

to correlate functional imaging features and pathological

characteristics of soft tissue sarcoma

Madelaine Hettler1; Julia Kitz2; Manuel Guhlich3; Ali Seif4; Jennifer Ernst5;

Lena-Christin Conradi1; Michael Ghadimi1; Philipp Ströbel2; Jens Jakob6

1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und

Kinderchirurgie, Göttingen, Deutschland

2Universitätsmedizin Göttingen, Institut für Pathologie, Göttingen, Deutschland

3Universitätsmedizin Göttingen, Klinik für Strahlentherapie und

Radioonkologie, Göttingen, Deutschland

4Universitätsmedizin Göttingen, Institut für Diagnostische und Interventionelle

Radiologie, Göttingen, Deutschland

5Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und

Plastische Chirurgie, Göttingen, Deutschland

6Universitätsmedizin Mannheim, Chirurgische Klinik, Mannheim, Deutschland

Background: Treatment and prognosis of so tissue sarcoma (STS) are

mainly based on histological subtype and grading. However, pretherapeu-

tic biopsies oen do not provide reliable tumor characterization due to

tumor size and intratumorale heterogeneity. By combining histopatho-

logic and functional imaging features the pretherapeutic grading might

be improved.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 231

Methods: Twelve patients with histologically conrmed STS were

included in the prospective pilot study. A preoperative diusion weighted

MRI was performed. Aer tumor resection, we collected core needle

biopsies (CNB) from several regions from the surgical specimen and le a

radiopaque marker at each biopsy site. Aerwards the markers were visu-

alized in a CT of the specimen. To evaluate the imaging features of the

exact sampling regions, fusion imaging of preoperative MRI and postop-

erative CT was performed. Grading by FNCLCC and apparent diusion

coecient (ADC) on functional MRI were determined for all specimens

and CNBs.

Result: In 7/12 cases, fusion imaging of pretreatment imaging and post-

operative CT of the resected specimen was feasible without relevant con-

tour deviations. Histological workup resulted in correct grading in 9/11

cases (81,8 %, in n=2: G1 instead of G2). Functional evaluation shows

a tendency for high-grade STS regions to have lower ADC values than

low-grade regions.

Discussion: Due to the challenging histopathological grading of STS,

there are already several attempts to develop a radiological grading.

However, these approaches currently do not provide suciently reliable

results. erefore, the supplementation of histopathological grading by

ADC is suggested to be a useful option to improve the grading of STS.

Conclusion: Our pilot study demonstrates the technical feasibility of cor-

relating fusion images of preoperative in situ MRI and postoperative CT

of the specimen. Further studies need to prove if functional imaging may

supplement histopathological grading.

Disclosure Statement: e authors declare no conict of interest.

341

Prognostic Factors and Survival of Patients with Uterine

Sarcoma – a German unicenter Analysis

Alexandra Huß1; Mir Fuad Hasanov1; Maximilian Klar1; Baonhan Hoang1;

Ingolf Juhasz-Böss1; Michaela Bossart2

1Uniklinik Freiburg im Breisgau, medizinische Fakultät, Klinik für

Frauenheilkunde, Freiburg im Breisgau, Deutschland

2St. Josefskrankenhaus Freiburg, Gynäkologie, Freiburg im Breisgau,

Deutschland

Background: is study aimed to describe the survival and identify prog-

nostic variables in patients with uterine sarcoma (US).

Methods: is unicentric, retrospective cohort study includes 57

patients with US over 18 years treated at the Department of Obstetrics

and Gynecology at University Hospital Freiburg between 1999 and 2017.

Progression-free survival (PFS) and overall survival (OS) were calculated

and visualized in Kaplan-Meier curves. Prognostic factors for total cohort

and Leiomyosarcoma (LMS) patients were identied using log-rank test

and Cox-regression.

Result: 44 LMS, seven low grade-endometrial stromal sarcoma (LG-ESS),

four high grade-ESS and two undierentiated US patients were identi-

ed. Median age at time of diagnosis was 51.0 years (range 1883). Median

follow-up time was 35 months. PFS for the total cohort was 14.0 months

(95%-Condence-Interval (CI) 9.7-18.3) and OS 36.0 months (95%-CI

22.149.9). LG-ESS was the most favorable histological subtype (OS 150.3

months). In the multivariate analysis, patients over 52 years showed a

four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-

CI 1.5-12.9). Progesterone receptor negativity was associated with a two

times higher risk for death (HR2.8; 95 %-CI 1.0-7.5). For LMS patients

age ≥52 years (p=0.04), surgical margin (p=0.01), FIGO stage (p=0.01)

and no application of chemotherapy (p=0.02) were statistically signicant

positive factors for OS.

Discussion: In this analysis, tumor histology, age at time of diagnosis

and progesterone receptor status were signicant prognostic factors for

US. Unfavorable OS in LMS patients was associated with advanced FIGO

stage, suboptimal cytoreduction and application of chemotherapy.

Conclusion: For this aggressive but rare tumor international prospec-

tive, multicenter databases are needed to provide more concordant data.

Consequent, standardized immunohistopathological workup as a basis

for molecular tumor boards is worthwhile.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

366

Personalized medicine for sarcoma patients – HERE, NOW

Manuela Regenbrecht1; Rica Sauer2; Maya Niethard3,4;

Christoph Reinhard5,6; Christian Regenbrecht5,6,7; Jürgen Loskutov6

1Helios Klinikum Berlin-Buch, Department of Oncology and Palliative Care,

Berlin, Deutschland

2Medizinisches Versorgungszentrum am Helios Klinikum Emil von Behring,

Institut für Gewebediagnostik / Pathologie, Berlin, Deutschland

3Helios Klinikum Berlin-Buch GmbH, Department for Tumor Orthopedics, Berlin,

Deutschland

4Greifswald University Hospital, Klinik und Poliklinik für Orthopädie und

Orthopädische Chirurgie, Greifswald, Deutschland

5ASC Oncology GmbH, Berlin, Deutschland

6CELLphenomics GmbH, Berlin, Deutschland

7Universitätsmedizin Göttingen, Department of Pathology, Göttingen,

Deutschland

Background: Sarcoma treatment is complicated by rarity of the disease

and its overwhelming complexity. e main therapeutical option for sar-

comas is surgery, adjuvant radiation and chemotherapy. In osteosarcoma

standard regimen has not changed over 4 decades(1, 2). Targeted thera-

peutic approaches are very limited and consist of imatinib and its analogs

in gastrointestinal stromal tumors and pazopanib(3). Overall, the current

landscape of sarcoma treatment options seems grim.

Methods:

Our group developed reverse clinical engineering approach for the sar-

comas, consisting of a robust 3D cell culture method (take rate ~80%)

and semi-automated high-throughput personalized toxicity testing(4).

is approach allows to facilitate selection of the best possible regimen

for sarcoma patients.

Result:

In close collaboration with Sarcoma Center Berlin-Brandenburg at Helios

Hospital Berlin-Buch we performed 5 personalized drug screens for the

patients with dierent types of sarcomas. e mean time between sample

processing and the test results was 37 days. For all patients we were able to

nd at least one single agent or combination, that were deemed ecient.

Discussion:

Further research and rigorous follow up is required for understanding of

the full potential of the reverse clinical engineering in sarcoma therapy.

However, even now it is obvious, that it can be used in cases with limited

options, such as clear cell sarcoma or cardiac angiosarcoma.

Conclusion:

• personalized drug screens for patients with dierent sarcoma subtypes

are possible.

• nding an ecient therapy regimen through reverse clinical engineer-

ing is possible.

• time frame for the drug screen is permissive for the use of the reverse

clinical engineering in decision making over the sarcoma patient drug

regimen.

Indication of source:

1. N. M. Marina et al., Lancet Oncol. 17, 1396–1408 (2016).

2. S. S. Bielack et al., J Clin Oncol. 33, 2279–2287 (2015).

3. T. G. Grünewald et al., Embo Mol Med. 12, e11131 (2020).

4. K. Boehnke et al., Slas Discov. 21, 931–941 (2016).

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts232

410

A cooperative registry of the Interdisciplinary German

Sarcoma group (AIO/ARO/CAO) to optimize either neo – or

adjuvant treatment strategies for adult patients (pts) with

large sized, high grade non-rhabdomyo(soft tissue)

sarcoma (STS)

J.T. Hartmann1; H.-G. Kopp2; Volker Budach3; Viktor Grünwald4; T. Wölfel5;

T. Kluba6; M. Rudert7; P.-U. Tunn8; I. Melcher9; O. Micke1; D. Kürschner10;

R. Herbst11; B. Hertenstein12; W. Blau13; F. Mayer14; A. Serrano1; J. Groth1;

A. Kunitz9

1Katholische Hospitalvereinigung Ostwestfalen, Bielefeld,

2Robert-Bosch-Krankenhaus, Stuttgart,

3Charité - Universitätsmedizin , Berlin,

4Universität, Essen,

5Universität, Mainz,

6Städtisches Klinikum, Dresden,

7Universität, Würzburg,

8Helios Klinikum, Berlin,

9Klinikum Spandau, Berlin,

10MVZ, Delitzsch,

11Klinikum , Chemnitz,

12Klinikum Mitte, Bremen,

13Dr. Horst Schmidt Kliniken , Wiesbaden,

14Praxis und Tagesklinik, Friedrichshafen,

Background: To examine whether concomitant chemotherapy and radia-

tion (RXT) achieves sucient DFS rates for pts with high risk adult-type

STS.

Methods: is is a prospective registry (IAWS-1/-2) at 40 centers. We

included pts with conrmed high risk (size > 5cm, G2/3, deep located)

STS, at least 18 yrs of age, normal organ functions, no evidence of dis-

tant mets. ey were assigned to either (arm 1) adjuvant or neoadjuvant

(arm 2) IFO-DOXO x 3 - IFO x 2 + RXT 50.4 Gy* – IFO-DOXO x 1 (*if

indicated/applicable, otherwise IFO-DOXO x 5) consisted of DOX 60 mg/

sqm i.v., on day 1, and IFO 3 g/sqm i.v., d1-3, qd22 (d1-2, qd22 concom-

itant to RTX). Primary aim was 5-yr DFS. Sample size was calculated to

achieve a power of 80% to detect a hazard ratio of 1.388, which corre-

sponds to the dierence in DFS of 65% vs. 55% compared to historical

controls. Ecacy analysis is based on ITT population. 274 pts have to be

assessed; secondary aims: ORR (in arm B), OS, dose intensity.

Results: Between 6/09 and 10/16 292 pts were either assigned to arm

1 (n=109) or arm 2 (n=183) depending on local tumor board decision;

275 pts have been treated per protocol; median age 50 yrs (18-70); m/f

56/44%; ECOG 0/1/2, 67/21/3%; location, extr/rp/centr/HNO/girdle,

53/21/12/6/4%; histo, pleoNOS/LS/other/SS/LMS, 28/20/15/11/11%; G

2/3, 29/70%; deep, 100%; med. Size, 9.5 cm; resection, n.d. 3.6%; R-status,

R0/1/2/unknown, 80/12/1/3%. 91 resp. 90% of pts underwent at least 3

cyc of DOX/IFO with higher dose reduction necessary due to IFO toxicity.

Discontinuation rate of CTX was 5.5%. RTX was applicable in 71% of pts.

Med. duration of f/u was 26.3 mos (0.9-165.6). 29.8% pts relapsed. 5-yr

DFS was 61.7% (95% CI: 49.6-73.9%) in arm 1 and 53.1% (95% CI: 41.3-

64.9%) in arm 2 with less events being observed during yrs 5-10. 5-yr OS

was 79.2% (95% CI: 68.9-89.6%) in arm 1 and 68.2% (95% CI: 57.4-78.6%)

in arm 2. Tumor reduction was seen in 52% of pts in arm 2.

Conclusions: CTX in close conjunction with RTX is an eective and fea-

sible approach in STS population when limited to high risk pts.

Indication of source: ESMO 2021

Disclosure Statement: e authors declare no conict of interest.

450

Value of local treatment modalities in patients with localized

Ewing Sarcoma. Report from the Ewing 2008 trial

Philip Heesen1,2; Andreas Ranft3,4; Vivek Bhadri5; Benedicte Brichard6;

Stephane Collaud4,7; Sona Cyprova8; Hans Eich9; Torben Ek10;

Hans Gelderblom11; Jendrik Hardes4,12; Lianne Haveman13;

Wolfgang Hartmann14; Peter Hauser15; Heribert Jurgens16; Jukka

Kanerva17; Thomas Kühne18; Anna Raciborska19; Jelena Rascon20;

Arne Streitbürger4,12; Beate Timmermann4,21; Yasmine Uhlenbruch22;

Uta Dirksen3,4

1University of Zurich, Faculty of Medicine

2University of Duisburg Essen, Pediatrics III

3University Hospital Essen, West German Cancer Center, Pediatrics III

4German Cancer Consortium, Partnersite Essen

5University of Sydney, Australia Faculty of Medicine and Health, Chris O´ Brien

Lifehouse

6Université Catholique de Louvain, Department of Pediatric Haematology and

Oncology

7University Hospital Essen, Department of Thoracic Surgery

8Motol Children´s Hospital, Charles University

9University Hospital Muenster, Radiotherapy and Radiooncology

10Queen Silvia Children´s Hospital, Childhood Cancer Center

11Leiden University Medical Center, Department of Medical Oncology

12University Hospital Essen, Clinic of Orthopedics

13Princess Máxima Center for Pediatric Oncology, Department of Solid tumors

14University Hospital Muenster, Gerhard Domagk Institute for Pathology

15Borsod-Abaúj-Zemplén County University Teaching Hospital, Velkey László

Child’s

16University Children’s Hospital Münster, Department of Pediatric Hematology

and Oncology

17HUS Helsinki University Hospital, New Children´s Hospital, Div. Hematology

and Stem Cell Transplantation

18University Children´s Hospital Basel

18 Department of Oncology/ Haematology, Basel,

19Mother and Child Institute, Department of Oncology and Surgical Oncology

for Children and Youth

20Vilnius University Hospital Santaros Klinikos, Center for Pediatric Oncology

and Hematology

21University Hospital Essen, Clinic for Particle Therapy, West German Proton

Beam Centre

22St. Josefs Hospital Bochum, University Hospital, Patient representative

Purpose: Local treatment is an essential element in the multimodal treat-

ment of Ewing sarcoma (EWS). e choice of a local control modality

for EWS is still controversial. Aim of our study was to analyze the impact

of local treatment modalities and clinical variables on overall survival in

patients treated according to the Ewing 2008 protocol.

Methods: e prospectively collected data of 833 patients with localized

EWS treated in the Ewing 2008 trial between 2009 and 2018 were analyzed.

All patients received induction chemotherapy prior to local treatment. We

tested proportional hazards assumption using Schoenfeld-residuals and

Goodness-of-t test, hazard ratios (HRs) with 95% Condence Intervals

were calculated using Cox regression. Log-rank test was performed.

Results: e 5-year survival probabilities were 0.84 (0.79, 0.89) for sur-

gery, 0.77 (0.69, 0.86) for radiotherapy and 0.84 (0.79, 0.88) for combina-

tion of surgery & radiotherapy, p=0.12.

e HR of radiotherapy vs surgery alone or combination of surgery and

radiotherapy was 1.23 (0.66, 2.30) for patients that had a small tumor vol-

ume (<200 mL) and 1.76 (0.90, 3.45) for patients that had a large tumor

volume (≥ 200 mL), aer adjusting for known prognostic factors as age

and tumor site. Detailed analysis of local treatment modalities in dierent

sites will be presented.

Discussion: OS was better in patients treated with surgery or surgery &

radiotherapy compared to radiotherapy alone, but this dierence was not

statistically signicant. OS might be increased in patients with large tumor

volume when treated with surgery or a combination of surgery & radio-

therapy compared to radiotherapy only.

Conclusions: Surgery and surgery & radiotherapy might be superior to

radiotherapy only. Treatment plans should consider our ndings, in line

with patient- characteristics and -preferences.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 233

593

There is no evidence for clinically relevant needle tract

seeding or abdominal recurrence following pre-treatment

biopsy of gastrointestinal stromal tumors (GIST) – results of a

systematic review

Jens Jakob1; Rashad Salameh2; David Wichmann1; Nicos Charalambous1;

Anne-Christine Zygmunt1; Michael Ghadimi1; Judith Heinz3; Ulrich

Ronellentsch4

1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral und

Kinderchirurgie

2Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Viszeral-, Thorax

und Gefäßchirurgie

3Universitätsmedizin Göttingen, Institut für Medizinische Statistik

4Universitätsklinikum Halle , Klinik für Viszerale, Gefäß und endokrine Chirurgie,

Halle (Saale), Deutschland

Background: No clear consensus exists if pre-treatment biopsy leads to

needle tract seeding or increase abdominal recurrence of GIST. e objec-

tive of this study was to estimate the risk of tumor recurrence associated

with pre-treatment core needle biopsy OR ne needle aspiration of gastro-

intestinal stromal tumors.

Methods: We performed a systematic literature search and included stud-

ies assessing the clinical and oncological outcome of GIST-patients who

underwent a pre-treatment core needle biopsy or ne needle aspiration.

We assessed methodological quality with the Newcastle-Ottawa-Scale for

non-randomized studies.

Results: Four non-randomized studies and seven case reports comprising

174 patients were eligible for inclusion. Needle tract seeding or abdominal

recurrence aer pre-treatment biopsy were primary endpoints in only two

trials. ere was no documentation of a single case of needle tract seeding.

None of the studies reported an increased rate of abdominal recurrence

aer pre-treatment biopsies.

Conclusion: ere appears to be no clinically relevant risk of needle tract

seeding or increased abdominal recurrence aer pre-treatment biopsy of

GIST.

Disclosure Statement: e authors declare no conict of interest.

628

DNA methylation-based classier and gene expression

signatures detect BRCAness in osteosarcoma

Maxim Barenboim1; Michal Kovac2; Baptiste Ameline3; David Jones4; Olaf

Witt5; Stefan Bielack6; Stefan Burdach7; Daniel Baumhoer3; Michaela

Nathrath8

1Technical University of Munich, Klinikum rechts der Isar, Department of

Pediatrics and Children’s Cancer Research Center, Munich, Deutschland

2Slovak University of Technology, Faculty of Informatics and Information

Technologies, Bratislava, Slovakia

3University of Basel, University Hospital Basel, Bone Tumour Reference Centre at

the Institute of Pathology, Basel, Schweiz

4Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Deutschland

5University Hospital Heidelberg, Department of Pediatric Oncology,

Hematology and Immunology, Heidelberg, Deutschland

6Klinikum Stuttgart – Olgahospital, Stuttgart Cancer Center, Pediatrics 5

(Oncology, Hematology, Immunology), Stuttgart, Deutschland

7Technical University of Munich, Institute of Pathology, Children’s Cancer

Research Center - Department of Pediatrics , Munich, Deutschland

8Klinikum Kassel, Department of Pediatric Oncology, Kassel, Deutschland

Background: Osteosarcoma (OS) is the most common primary malig-

nant bone tumour. BRCAness is a phenotypical trait in tumors with defect

in homologous recombination (HR) repair resembling tumors with inac-

tivation of BRCA1/2 rendering these tumors sensitive to poly-(ADP)-ri-

bose polymerase inhibitors (PARPi). Recently, OS was shown to exhibit

molecular features of BRCAness. Our goal was to develop a method com-

plementing existing genomic methods to aid clinical decision making on

administering PARPi in OS patients.

Methods: OS samples with DNA-methylation data were divided to

BRCAness-positive and negative groups based on degree of their genomic

instability (n=41). Methylation probes were ranked according to decrease

variance dierence between two groups. Top 2000 probes were selected

for training and cross-validation of random forest (RF) algorithm. Two

third of available OS RNA-Seq samples (n=17) from the top and bottom

of sample list ranked according to genome instability score were subjected

to dierential expression (DE) and, subsequently, to gene set enrichment

analyses (GSEA).

Result: Combined accuracy of trained RF was 85% and the average of area

under the ROC curve was 0.95. ere were 449 upregulated and 1,079

downregulated genes in BRCAness-positive group (fdr<0.05). GSEA

of upregulated genes detected enrichment of DNA replication and, of

note, mismatch repair and HR signatures (FWER<0.05). Validation of

BRCAness classier with independent OS set (n=20) showed AUC of 0.87

with accuracy of 90%.

Discussion: e RF classier can identify BRCAness cost-eective since

it does not require sequencing of control tissue DNA. HR gene expres-

sion signature was identied for the rst time in OS. e low frequency

of BRCA1/2 mutations in OS implies that the increased presence of

BRCAness in OS arises from alterations in other genes of the HR pathway.

Conclusion: We developed a new classier based on DNA-methylation

patterns that detects BRCAness in OS samples with high accuracy. is

approach can be extended to cancers characterized by genome instability

(PMID: 34762643).

Disclosure Statement: e authors declare no conict of interest.

749

Convergent genetic mechanisms drive EIF4EBP1

overexpression, translational deregulation and tumorigenesis

in Ewing sarcoma

Cornelius Funk1,2; Martin F. Orth3; Karim Aljakouch4; Jing LI1,2;

RolandImle2,5; Laura Romero-Perez1,2; Tilman L. B. Hölting3;

Maximilian M. L. Knott3; Aruna Marchetto3; Felina Zhanow1,2; Ana Sastre6;

Javier Alonso7,8; Rainer Will9; Felix Bestvater10; Thomas Kirchner3;

Olaf Witt2,11; Ina Oehme2,11; Ana Banito2,5; Gabriel Leprivier12;

Wolfgang Hartmann13; Uta Dirksen14; Stefan M. Pster2,15;

Jeroen Krijgsveld4; Florencia Cidre-Aranaz1,2; Thomas G.P. Grünewald1,2,3;

Julian Musa1,2,16

1Deutsches Krebsforschungszentrum, Division of Translational Pediatric

Sarcoma Research, Heidelberg, Deutschland

2Hopp Children’s Cancer Center (KiTZ), Heidelberg, Deutschland

3Institute of Pathology, Faculty of Medicine, LMU Munich, Max-Eder Research

Group for Pediatric Sarcoma Biology, München, Deutschland

4Deutsches Krebsforschungszentrum, Proteomics of Stem Cells and Cancer,

Heidelberg, Deutschland

5Deutsches Krebsforschungszentrum, Soft-Tissue Sarcoma Junior Research

Group, Heidelberg, Deutschland

6Hospital Infantil Universitario La Paz, Unidad hemato-oncología pediátrica,

Madrid, Spanien

7Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid,

Spanien

8Instituto de Investigación de Enfermedades Raras, Unidad de Tumores Sólidos

Infantiles, Madrid, Spanien

9Deutsches Krebsforschungszentrum, Genomics & Proteomics Core Facilities

TP3, Heidelberg,

10Deutsches Krebsforschungszentrum, Light Microscopy Facility (W210),

Heidelberg, Deutschland

11Deutsches Krebsforschungszentrum, Pediatric Oncology (B310), Heidelberg,

Deutschland

12Institute of Neuropathology, Medical Faculty, University Hospital Düsseldorf,

Düsseldorf, Deutschland

13Division of Translational Pathology, Gerhard-Domagk Institute of Pathology,

University Hospital of Münster, Münster, Deutschland

14Department of Pediatric Hematology and Oncology, University Hospital of

Essen, Essen, Essen, Deutschland

15Deutsches Krebsforschungszentrum, Division of Pediatric Neuro-Oncology,

Heidelberg, Deutschland

16Universitätsklinikum Heidelberg, Department of General, Visceral and

Transplantation Surgery, Heidelberg, Deutschland

Background: Ewing sarcoma (EwS) is an aggressive pediatric bone can-

cer characterized by a chromosomal translocation fusing the EWSR1 gene

to various members of the ETS family of transcription factors – most

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts234

commonly FLI1. EWSR1-FLI1 acts as an oncogenic transcription factor

driving EwS malignancy. Additional mutations in EwS are rare, however

50% of EwS cases include gains of chr8. EIF4EBP1, a major mTORC1

downstream target and chr8 gene, encodes for a translation initiation fac-

tor with controversial roles in tumorigenesis.

Methods: Using a variety of bioinformatic analyses and functional in vitro

and in vivo experiments and pSILAC mass spectrometry, we characterized

EIF4EBP1 in EwS.

Result: Screening a microarray gene expression dataset of 196 EwS tumors

with matched clinical data, we identied EIF4EBP1 as the one being most

strongly associated with patients´ overall survival among all chr8 genes.

Silencing of EWSR1-FLI1 in 14 EwS cell lines led to a downregulation of

EIF4EBP1, which was validated in vivo. Knockdown of EIF4EBP1 lead to

signicantly decreased cell proliferation, 2D clonogenic and 3D anchor-

age-independent growth of EwS cell lines and similarly reduced growth

of EwS xenogras. Proteomic proling using pSILAC mass spectrome-

try in EIF4EBP1 silenced EwS cell lines identied dierentially expressed

proteins being strongly enriched in respiratory chain and oxidative phos-

phorylation proteins.

Discussion: Our data clearly supports an oncogenic role of EIF4EBP1

in EwS and highlights the hitherto not suciently appreciated aspect of

translational deregulation in Ewing sarcomagenesis. Moreover, our study

highlights the EIF4EBP1-mediated prognostic relevance of chr8 gains in

EwS.

Conclusion: EIF4EBP1 is a prognostically relevant gene, which is upregu-

lated in EwS by both, EWSR1-FLI1 and chr8 gains and which contributes

to proliferation and clonogenic growth of EwS cells in vitro and in vivo,

likely due to translational deregulation of proteins involved in oxidative

phosphorylation.

Disclosure Statement: e authors declare no conict of interest.

765

Eects of an individualized exercise intervention on gait

function in adolescents and young adults (AYA) with tumor

endoprosthesis of the lower extremity - a pilot RCT (proGAIT)

Simon Basteck1,2; Wiebke Guder3; Uta Dirksen1,2; Arno Krombholz4;

Miriam Götte1,2

1Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Klinik für

Kinderheilkunde 3

2Deutsches Konsortium für Translationale Krebsforschung, Standort Essen

3Universitätsklinikum Essen, Klinik für Tumororthopädie und Sarkomchirurgie

4Ruhr-Universität Bochum , Fakultät für Sportwissenschaft

Background: Limb preservation using endoprosthesis in bone tumor

patients is in some cases contrasted by signicant functional limitations

and gait abnormalities. Primary aim of the proGAIT-RCT was to evaluate

the eectiveness of an exercise intervention on gait function in AYA can-

cer survivors with tumor endoprosthesis.

Methods: N = 11 cancer survivors with a mean age of 26.6. (±8.4) years

and a mean follow-up since tumor endoprosthesis implantation around

the knee of 4.9 (±4.9) years were randomized to an intervention group

that received a partially supervised individualized 8-week exercise pro-

gram or a control group. Gait function was assessed via 3D gait analy-

sis. Secondary outcomes were QoL, fatigue, and functional performance

assessed via questionnaires and functional tests.

Results: e exercise intervention had small to medium eects on gait

score GDI |d|=0.50 (unaected leg), |d|=0.24 (aected leg), subjective

functional scores TESS |d| = 0.74 and MSTS |d| = 0.49 and functional

tests TUG and TUDS |d| = 0.61 and|d| = 0.52. Fatigue changed in favor

of the control group (|d| = 0.85). None of these changes showed statistical

signicance. No adverse events occurred.

Discussion: Promising intervention eects lead to the assumption that

exercise interventions could make an important contribution to improve

lower limb function and patient related outcomes in AYA cancer survivors

with tumor endoprosthesis. Because of the small sample size in this pilot

study, none of the changes were signicant.

Conclusion: e proGAIT study addresses a relevant research gap and

probably initiates a powered RCT as a follow-up project. Particular eorts

should be made to improve exercise-related follow-up care for aected

patients.

Disclosure Statement: e authors declare no conict of interest.

801

Multipel rezidivierendes und kurativ wiederholt reseziertes

retroperitoneales Liposarkom - 20 Jahre nach Erstdiagnose

bei stabiler pathohistologischer Morphe jedoch wechselndem

Grading (außergewöhnlicher Fallbericht)

Regina Moritz-Tugral1; Hans-Ulrich Schulz2; Dörthe Jechorek1;

Frank Meyer3

1Institut für Pathologie, Universitätsklinikum Magdeburg A.ö.R., Magdeburg,

Deutschland

2Klinik für Allgemein- und Viszeralchirurgie, AMEOS-Klinikum Haldensleben,

Haldensleben, Deutschland

3Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie,

Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland

Ziel: Illustration d. außergewöhnl. Casus eines retroperit. Liposarkoms,

welches trotz init. R0-Resektion vor 20 Jahren mehrfach rezidivierte

(Tumor[Tu]-Manifestationen: n=18). Der seltene langfristig-klin.

Verlauf wurde anhand d. diagnost. sowie pathomorphol. & histol.

Tu-Eigenschaen sowie der jeweiligen Spezikationen d. jeweils nur mit-

telfristig Tu-freien “Outcomes” aufgearbeitet.

Kasuistik: Ein inzw. 70-jähriger Mann wurde inital mit einem

23x29x15 cm großen retroperit. Liposarkom links diagnostiziert & b.

Ersteingri R0-reseziert.

In der Tu-Nachsorge wurden insges. 14 retro- & 4 intraperit.

Tu-Rezidive innerhalb v. 10 Episoden eines erneut aufgetretenen

Tu-Wachstums (durchschnittl. Tu-freie Zeitdauer: 20,04 [range: 12,64–

36,04] Monate) diagnostiziert. Bei allen Folgeeingrien konnte stets in

kurativer Intention überwiegend R0-reseziert bzw. im Folgeeingri –

nachreseziert werden. Die durchschnittl. Präparategröße betrug 8,065

(range: 1,7–29)cm.

Die Histologie zeigte initial ein Liposarkom G3 - b. den Tu-Rezidiven

bestätigte sich jeweils das Liposarkom (variierendes G). Durch das

teils verdrängende Tu-Wachstum wurden mehrfach auch multivisz.

Resektionen d. paarigen & unpaaren Bauchorgane notw., wobei der-

zeit eine chron., Tu-resezierend induz. enterokut. Fistel nach letzter

Tu-Resektion vor >12Monaten vorliegt (mit Colostomabeutel versorgt).

Schlussfolgerung: Die chir. Resektion unter kurativer Intention ist auch b.

Liposarkomrezidiv eine aussichtsreiche er.-Option, da b. jeweils errre-

ichtem R0-Status auch b. multipel rekurrentem Liposarkom ein mittel- bis

langfristiges, Tu-therapeut. beherrschbares Outcome mit signif. Tu-freien

Perioden erreicht werden kann. Dies wird eindrucksvoll & erstmals in

einer deratigen Eingris- & Präparateserie im vorgest. spektakulären

Fall demonstriert. Bei dieser Sarkomentität erscheint das Tu-Rezidiv-

assoziierte, prognost. eher günstigere G1/G2 diesen Langzeitverlauf zu

begünstigen. Eine engmaschige kiln. & bildgebende Tu-Nachsorge ist

hierfür unerlässlich.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 235

Skin Cancer including Melanoma

Poster

Encorafenib plus binimetinib in patients with locally

advanced, unresectable or metastatic BRAFV600-mutated

melanoma: an ongoing multi-centric, multi-national,

prospective, longitudinal, non-interventional

study – BERING-Melanoma

Dirk Schadendorf1; Erika Richtig2; Carmen Loquai3; Andrea Forschner4;

Ralf Gutzmer5; Sebastian Haferkamp6; Jochen Utikal7;

Jessica Cecile Hassel8; Friedegund Meier9; Dirk Debus10; Michael Fluck11;

Daniela Goeppner12; Helmut Kehrer13; Reinhard Dummer14;

Roger von Moos15; Jan Thompson16; Laura Gengenbacher17;

Olivier Michielin18; Christoph Hoeller19

1Department of Dermatology, University Hospital Essen, Essen, Deutschland

2Department of Dermatology, University of Graz, Graz, Österreich

3Department of Dermatology, University Medical Center Mainz, Mainz,

Deutschland

4Department of Dermatology, University Hospital of Tuebingen, Tuebingen,

Deutschland

5Department of Dermatology, Mühlenkreiskliniken Minden, Ruhr University

Bochum, Minden, Deutschland

6Department of Dermatology, University Hospital of Regensburg, Regensburg,

Deutschland

7Skin Cancer Unit, DKFZ and Medical Faculty Mannheim of Heidelberg

University, Mannheim, Deutschland

8Department of Dermatology, Heidelberg University Hospital, NCT Heidelberg,

Heidelberg, Deutschland

9Department of Dermatology, University Hospital Carl Gustav Carus, Dresden,

Deutschland

10Department of Dermatology, Nuremberg General Hospital, Paracelsus Medical

University, Nuremberg, Deutschland

11Department of Internal Medicine, Fachklinik Hornheide, Muenster,

Deutschland

12Department of Dermatology, University Hospital of Giessen, Giessen,

Deutschland

13Department of Dermatology, Ordensklinikum Linz Elisabethinen, Linz ,

Österreich

14Department of Dermatology, University Hospital of Zurich, Zurich, Schweiz

15Department of Medical Oncology, Kantonsspital Graubuenden, Chur, Schweiz

16Alcedis GmbH, Giessen, Deutschland

17Pierre Fabre Pharma GmbH, Freiburg, Deutschland

18Center of Personalized Oncology, Lausanne University Hospital (CHUV),

Lausanne, Schweiz

19Department of Dermatology, Medical University of Vienna, Vienna, Österreich

Background: For the treatment of locally advanced, unresectable or met-

astatic BRAFV600-mutated melanoma, targeted therapy with a combina-

tion of BRAF and MEK inhibitors represents a standard of care.

e combination therapy of encorafenib plus binimetinib was approved

in the EU in Sep 2018 and in Switzerland in Nov 2019. e approval was

based on positive results from the COLUMBUS study, with a median pro-

gression-free survival (PFS) of 14.9 mo (5-year PFS: 23%) and a median

overall survival (OS) of 33.6 mo (5-year OS: 35%). e observed tolerabil-

ity prole consisted of the expected adverse events of this substance class.

Methods: BERING-Melanoma is an ongoing, multi-national, multi-cen-

tric, prospective, longitudinal, non-interventional study (NIS). e proj-

ect aims to enroll up to 750 patients at a total of 80 German, Austrian and

Swiss sites with a total study duration of approx. 8 yrs. From Oct 2019 to

mid Apr 2022, 308 patients have been included.

Result: e NIS analyses the ecacy, quality of life, safety and tolerability

of treatment with encorafenib + binimetinib in advanced, unresectable

or metastatic BRAFV600-mutated melanoma under real-world condi-

tions. e study focuses on the documentation of rst- and second-line

treatment (i.e. aer one line of prior checkpoint inhibition therapy in the

advanced setting) and patients treated according to the SmPC (Summary

of Product Characteristics). e primary objective is to collect data on the

1-year PFS rate. In addition, the inuence of prognostic factors on ecacy,

safety and tolerability is investigated.

Discussion: Since data from controlled clinical trials are based on a

selected patient population, the present NIS investigates the use of

encorafenib + binimetinib under real-world conditions in a broader

patient population.

Conclusion: At this year’s DKK Congress, the inclusion process as well as

current data on the baseline characteristics of the included patients will be

presented. e NIS is sponsored by Pierre Fabre Pharma.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

267

Use of nivolumab (NIVO) in adjuvant melanoma patients:

real world data from NICO, a national prospective non-

interventional study

Ralf Gutzmer1; Peter Mohr2; Thomas Eigentler3; Imke Grimmelmann4; Lisa

Zimmer5; Elisabeth Livingstone5; Selma Ugurel5; Jochen Utikal6; Verena

Müller6; Daniela Göppner7; Rudolf Herbst8; Alexander Kreuter9; Claudia

Pföhler10; Wiebke Hollburg11; Loquai Carmen12; Martin Herber13; Katharina

C. Kähler14; Michael Weichenthal14; Dirk Schadendorf5

1Mühlenkreiskliniken AöR, Universitätsklinikum der Ruhr-Universität, Minden,

Deutschland

2Elbe-Kliniken Buxtehude, Buxtehude, Deutschland

3Charité - Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und

Allergologie, Berlin, Deutschland

4Medizinische Hochschule Hannover, Haut-Tumor-Zentrum, Hannover,

Deutschland

5Universitätsklinikum Essen, Essen, Deutschland

6Deutsches Krebsforschungszentrum (DKFZ) und Universitätsklinikum

Mannheim, Ruprecht-Karl Universität Heidelberg, Mannheim,

7Justus-Liebig-Universitat Gießen, Gießen, Deutschland

8Helios Klinikum Erfurt, Erfurt, Deutschland

9Helios St. Elisabeth Klinik, Oberhausen, Deutschland

10Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland

11Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Deutschland

12Universitätsmedizin Mainz, Hautkrebszentrum Rhein-Main, Mainz,

Deutschland

13Bristol Myers Squibb, München, Deutschland

14Universitätsklinikum Schleswig-Holstein, Kiel, Deutschland

Background: e phase 3 CM 238 trial demonstrated durable clinical

benet for NIVO in patients with resected stage III B/C or IV melanoma,

and NIVO has become a standard treatment for resected melanoma.

Additional real-world data on eectiveness and tolerability are warranted

and are collected in NICO, a prospective, non-interventional study in

Germany associated to ADOREG.

Methods: NICO (NCT02990611) consists of 3 cohorts: patients with

either advanced melanoma who started therapy with NIVO+IPI or NIVO

(cohort 1 and 2) or patients with resected Stage III/IV melanoma treated

with NIVO in the adjuvant setting (cohort 3). Patients in all cohorts are

followed for up to 5 years. Relapse-free survival is the primary objective

for cohort 3. We report data from the second interim analysis of cohort 3

(database lock: 31 January 2022) focusing on baseline patient character-

istics and safety.

Result: Baseline data were available for 331 patients in cohort 3. Median

age of patients was 64 years (range, 23-94), and 59% were male. Almost all

patients (92%) had ECOG score < 2 (8% unknown), and 9%, 30%, 44%,

2% and 13% had stage IIIA, IIIB, IIIC, IIID, and IV disease (AJCC, 8th

edition), respectively. At initial diagnosis, 27% of patients enrolled in this

study had BRAF mutant melanoma, and 52% had BRAF wildtype (21%

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts236

unknown). To date, 346 treatment-related adverse events (TRAE) were

reported [grade 1/2: 273 (79%); grade 3: 45 (13%); grade 4: 11 (3,2%);

grade 5: 1 (< 1%); missing grade: 16 (4,6%)]. At least one non-serious

treatment-related AE was reported in 129 (39,1%) patients, and one seri-

ous TRAE in 42 (12,7%) patients. 13,9% of patients discontinued due to

TRAE. Median time on study is 18,2 months (11.9-12.7), and 8,8% of the

patients are still on treatment.

Discussion: is study of adjuvant NIVO treatment in a real-world set-

ting supports the known safety prole of NIVO in a less selected patient

population compared to clinical trials. Preliminary data on AE occurrence

reect the known NIVO safety prole.

Conclusion: is data provides valuable insight in the current use of

NIVO in the adjuvant setting.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

544

Retrospective Single Case Reports on the Treatment of

Advanced BRAFV600-mutated Malignant Melanoma with

Encorafenib plus Binimetinib (REMINISCENCE)

Dirk Debus1,2; Mareike Alter1; Marie-Therese Dernoscheg2; Peter Rohrer2;

Lukas Koch2; Van Anh Nguyen3; Patrick Terheyden4

1Universitätshautklinik, Universitätsklinikum Magdeburg, Magdeburg,

Deutschland

2Universitätsklinik für Dermatologie & Venerologie, Medizinische Universität

Graz, Graz, Österreich

3Universitätsklinik für Dermatologie, Venerologie & Allergologie, Medizinische

Universität Innsbruck, Innsbruck, Österreich

4Klinik für Dermatologie, Allergologie & Venerologie, Universitätsklinikum

Schleswig-Holstein, Lübeck, Deutschland

Background: Challenges for the treatment of advanced, unresectable or

metastatic BRAFV600 mutated melanoma include the denition of an opti-

mal therapy sequence. is project aims to collect case reports of patients

(pts) with remarkable treatment courses for training purposes and scien-

tic discussion.

Methods: Cases of adult pts with advanced, unresectable or metastatic

BRAFV600 mutated melanoma with a therapy sequence including ongo-

ing or completed encorafenib/binimetinib (EB) were selected by treating

physicians. Aer written informed consent data of eligible pts were docu-

mented retrospectively using standardized case report forms.

Result: In total, 17 pts from 5 centers in Germany and Austria were

included. Five cases will be presented: 1) female, 64 yrs, long-lasting com-

plete response (CR) under 1st-line EB therapy in the metastatic setting

(treatment duration [TD] at cut-o: 5.6 yrs); 2) male, 53 yrs, advanced

setting including brain metastases, complex prior therapy lines, EB in

late therapy line with partial response (PR) and parallel CNS surgery (TD

at cut-o: 1.4 yrs); 3) female, 82 yrs, poor prognosis (brain metastasis,

increased LDH and concomitant autoimmune disease), 1st-line EB ther-

apy with PR aer surgical intervention and stereotactic radiotherapy (TD

at cut-o: 1 yr); 4) female, 88 yrs, diverse (oncologic) concomitant dis-

eases, initial curative approach, EB therapy in 1st-line in the advanced

setting with CR and adequate tolerability limited to mainly gastrointesti-

nal side eects (TD at cut-o: 1.1 yrs); 5) female, 71 yrs, increased LDH,

2nd-line EB therapy with stable PR (TD at cut-o 1.2 yrs) following rapid

progression under rst-line nivolumab therapy.

Discussion: ese insights into clinically relevant therapeutic approaches

could serve to establish a basis for discussion on therapy management and

sequence between medical experts.

Conclusion: All 5 patients presented with heterogenous therapy courses

and show a relevant therapy benet along with adequate tolerability

during EB therapy.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

648

First results of a clinical study investigating hearing and

hearing impairment in melanoma patients under therapy with

checkpointinhibitors or BRAF and MEK inhibitors

Claudia Pföhler1; Julia Ehrmann1; Roman Saternus1; Anne-Catherine

Wagner1; Krista Yordanova1; Leonie Adam1; Bernhard Schick2;

Thomas Vogt1; Gentiana I. Wenzel2

1Universitätsklinikum des Saarlandes, Klinik für Dermatologie

und Hauttumorzentrum, Homburg/Saar, Deutschland

2Universitätsklinikum des Saarlandes, Klinik für Hals-, Nasen- und

Ohrenheilkunde, Homburg,

Background: Checkpointinhibitors (CPI) may lead to immune-related

side eects (irAEs). e development of some irAEs such as therapy-in-

duced vitiligo could be associated with clinical benet in the context of

CPI treatment. CPI treatment may also lead to the production of anti-

bodies against retinal or inner ear antigens inducing impairment of vision

and hearing as described previously. Patients with vitiligo may suer from

hearing impairment resulting from an aection of pigmented cells in the

inner ear.

Methods: We investigated 93 melanoma patients (m=57, f=36, median

age 64 years) who received nivolumab (n=37), pembrolizumab (n=28),

a combination of ipilimumab and nivolumab (n=3) or a combination

of BRAF- /MEK inhibitors (n=14) due to stage III or IV melanoma. All

patients received audiometric assessment. 27 patients received a re-test.

Results: 15/93 of the patients reported an already diagnosed hearing

impairment that could be veried by audiometry. We diagnosed in 60/93 a

so far unknown hearing impairment and only 18/93 had normal hearing.

13/93 patients developed therapy-induced vitiligo. From 27 patients that

were re-tested, six presented a sensorineural hearing loss of at least 10 dB

in at least one frequency at and above 3 KHz. Out of these one case was

aected bilaterally in the rest of 5 were aected just single sided.

Discussion: e high number of melanoma patients with unknown

hearing impairment is noticeable. However, it remains unclear if hearing

impairment results from melanoma disease or its treatment or if hearing

impairment is basically underdiagnosed in this population group. It is

imaginable that therapy-induced vitiligo is associated with the develop-

ment of hearing impairment.

Conclusion: Further studies are warranted to investigate hearing before,

under and aer therapy with CPI or BRAF-/MEK inhibitors. is might

allow to recognize early and monitor the evolution of therapy-induced

hearing impairment as well as to assess possible adjustments of therapeutic

regimens.

Disclosure Statement: e authors declare the following: CP received honoraria

(speaker honoraria or honoraria as a consultant) and travel support from Novartis,

BMS, Roche, Merck Serono, MSD, Celgene, AbbVie, SUNPHARMA, Pierre Fabre

and LEO

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 237

959

Chernobyl‘s Aftermath: Multiple manifestations of basalioma

in a patient after radioactive contamination in 1986

Marcel Ebeling1; Konrad Steinestel2; Michael Grunert3; Frank Wilde4

1German Armed Forces Hospital Ulm, Department of Oral and Plastic

Maxillofacial Surgery, Ulm, Deutschland

2German Armed Forces Hospital Ulm, Institute of Pathology and Molecular

Pathology, Ulm, Deutschland

3German Armed Forces Hospital, Department of Nuclear Medicine, Ulm,

Deutschland

4University Hospital Ulm, Department of Oral and Plastic Maxillofacial Surgery,

Ulm, Deutschland

Background: e Chernobyl nuclear disaster is considered the worst

nuclear accident in history. In 1986, two explosions at the reactor in

Pripyat, Ukraine resulted in the destruction of the reactor core and unhin-

dered release of radioactive particles. Radioactivity is a risk factor for the

development of basal cell carcinoma (BCC), since radiation-induced

mutations in both Sonic hedgehog (Shh) signaling pathway genes and

TP53 have been described.

Methods: We present the case of a patient with a history of radiation

exposure upon the 1986 Chernobyl accident who presented to our outpa-

tient clinic with recurrent BCCs in the facial region.

Result: e patient presented to our clinic with two facial lesions suspi-

cious for BCC. Although there were no typical risk factors, yet 11 BCCs

had previously been removed. Staging using an 18F-FDG-PET/CT as well

as ultrasound of the abdomen revealed no other tumor manifestations,

except for a lymph node which showed no signs of malignancy upon ne

needle biopsy.Diagnostic excision of the two facial lesions was performed,

and histopathological workup revealed BCC at the right temporal region

and acanthopapillomatosis at the corner of the mouth. Aer presentation

to the tumor board, complete resection of the basal cell carcinoma was

initiated. e patient remains attached to our hospital for follow-up.

Discussion: Despite contradictory studies, there are clear indications that

radioactive radiation must be assumed to play a role in the development

of BCCs. is must be considered due predisposing factors such as muta-

tions in the PTCH gen, p53 mutations, chronic exposure to UV radiation,

or autosomal dominant inherited tumor syndromes such as Gorlin-Goltz

syndrome.

Conclusion: is case demonstrates the value of early use of 18F-FDG-

PET/CT in staging/restaging to visualize BCC location, local spread,

potential metastases, secondary tumors and to aid in the decision of ther-

apeutic management. Furthermore, it underlines that long-term eects of

ionizing radiation should be considered in the diagnosis and management

of malignant skin tumors.

Disclosure Statement: e authors declare no conict of interest.

Supportive Care

Best-of-Abstract-Vortrag

356

Eects of a specic strength training on self-reported

activities of daily living, physical activity and motor

performance among children and adolescents with leukemia

or non-Hodgkin lymphoma: ndings of the randomized

controlled ActiveADL Study

Dominik Gaser1,2; Christiane Peters2; Renate Oberhoer-Fritz2; Miriam

Götte3; Irene Schmid4; Tobias Feuchtinger4; Irene Teichert-von Lüttichau1;

Sabine Kesting1,2

1Kinderhämatologie und –Onkologie, Kinderklinik München Schwabing,

Klinik und Poliklinik für Kinder- und Jugendmedizin, Klinikum rechts der Isar,

Technische Universität München, München, Deutschland

2Lehrstuhl für Präventive Pädiatrie, Fakultät für Sport- und

Gesundheitswissenschaften, Technische Universität München, München,

Deutschland

3Pädiatrische Hämatologie und Onkologie, Klinik für Kinderheilkunde III,

Universitätsklinikum Essen , Essen, Deutschland

4Zentrum für Pädiatrische Hämatologie und Onkologie, Kinderklinik und

Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universität

München, München, Deutschland

Background: Due to treatment- and disease-related side eects, chil-

dren undergoing cancer treatment show reduced physical activity (PA)

and muscular decits that can limit the autonomous accomplishment of

activities of daily living (ADLs). Increased muscle strength and regular PA

are related to cope with ADLs and thus can provide the greatest possible

autonomy during treatment. However, eects of strengthening exercises

on ADL accomplishment have not yet been examined.

Methods: In this bicentric RCT, we recruited patients (4-18 years) diag-

nosed with acute leukemia or NHL. e control group (CG) was provided

a standard care sports program. e Intervention group (IG) received

standard care combined with a specic strength training. For both groups,

exercise interventions were scheduled 2-3 days per week. At four measure-

ment points, we assessed physical function limitations using the Activities

Screen, PA level using an accelerometer and motor performance with the

MOON-test.

Results: Over a span of 34 months, we included 41 participants (10.0±4.0

years; 66% male; IG n=21) 15.1±10.2 days post-diagnosis. During the

mean intervention period of 7.4±2.4 months, participants completed

37±21 training sessions, with 29.7±4.7 min on average. Both groups

scored similar cross-sectional and longitudinally increased ASK scores

(IG: 64.6±19.2à85.4±24.3; CG: 68.1±20à86±12.2). Motor performance

was reduced in nearly all abilities compared to reference values. At nal

assessment, IG showed slightly improved motor abilities compared to CG.

Discussion: Functional limitations regarding the ADLs are indicated early

aer diagnosis. Instructed training interventions during acute treatment

support the patient’s mobility. IG participants show remarkable compli-

ance with strength training.

Conclusion: Our results illustrate that pediatric cancer patients need

access to structured, holistic exercise programs to maintain physical per-

formance, autonomy and activity level over the period of acute treatment.

Disclosure Statement: e authors declare no conict of interest.

791

Evaluation of the eects of a 6-months telemedicine based

exercise intervention on cardiorespiratory tness and quality

of life in cancer survivors

Verena Krell1; Johanna Porst1; Franziska Greiß1; Bernd Wolfarth1

1Charité Universitätsmedizin Berlin, Abteilung Sportmedizin, Berlin,

Deutschland

Background: ere is strong evidence of the benecial eects of physical

activity on physical performance and quality of life in cancer survivors.

Yet, the usual care regarding exercise therapy aer cancer diagnosis is

lacking especially in sparsely populated regions. e aim of this study is

to evaluate the eects of a telemedicine based exercise intervention on

cardiorespiratory tness and quality of life.

Methods: e study is designed for cancer survivors (CS) who have

completed their acute cancer therapy. Based on spiroergometry patients

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts238

of the intervention group (IG) receive an individual training plan with

overall goal of at least 150 minutes physical activity per week. Training

adherence is telemedically recorded and supervised through an activity

tracker. Patients of the control group (CG) receive group exercise therapy

for CS. Primary endpoint is cardiorespiratory tness (VO2peak) measured

at three time points (V0: baseline; V1: aer 6 months intervention; V2:

Follow up aer 12 months). Secondary endpoint is quality of life (QoL)

assessed by questionnaire EORTC QLQ-C30.

Result: Mean relative VO2peak was 25,8±7,1 ml/min/kg for patients of

IG (n=28) and showed no signicant change from V0 to V1. Despite this

there was a signicant change in relative maximum power (Pmax) from

baseline to V1 (p<0,05). For patients of CG (n=15) mean relative VO2peak

was 18,1±3,6 ml/min/kg. In this group neither relative VO2peak nor rela-

tive Pmax changed signicantly from V0 to V1. In IG QoL scale physical

functioning improved signicantly from V0 to V1 (p<0,05). In CG there

was no signicant change in QoL measured.

Discussion: e preliminary evaluation of the telemedicine based exer-

cise intervention shows no improvement on overall cardiorespiratory t-

ness but on QoL scale physical functioning. is indicates that physical

functioning does not only rely on the assumed improvement of cardiore-

spiratory tness.

Conclusion: In order to compare a telemedicine based exercise interven-

tion with group exercise therapy for CS further analyses with higher num-

ber of cases are required.

Disclosure Statement: e authors declare no conict of interest.

1036

A Novel, Long-Acting G-CSF Fusion Protein without

PEGylation in Women with Breast Cancer Receiving

Myelotoxic Chemotherapy – Results of a Pivotal Randomized,

Controlled Clinical Trial

Hartmut Link1; John Glaspy2; William Daley3; Igor Bondarenko4;

Dean Rutty5; Jianmin Chen3

1Hämatologie Internistische Onkologie, Kaiserslautern, Deutschland

2Ronald Reagan UCLA Medical Center, Los Angeles, USA

3Evive Biotechnology Inc, Bridgewater, USA

4Dnipro State Medical University, Dnipro, Ukraine

5Everest Clinical Research, Markham, Ontario, Kanada

Background: Chemotherapy-induced neutropenia (CIN) is the primary

dose-limiting toxicity in patients (pts) receiving myelotoxic chemother-

apy (CTX). Eemalenograstim alfa (F-627) is a novel, non-pegylated,

recombinant fusion protein containing human G-CSF and an IgG2-Fc

fragment, which is intended to reduce CIN by stimulating neutrophilic

proliferation and activation. e study (NCT03252431) evaluated the e-

cacy and safety of F-627 compared to the pegylated lgrastim (PEG-FIL)

Neulasta®.

Methods: 393 female pts with stage I - III breast cancer receiving 4 cycles

of myelotoxic CTX were randomized to F-627 or PEG-FIL (1:1 ratio) and

received the study drug 24 h s.c. aer the last day of CTX administration.

e primary ecacy endpoint was the duration of Grade 4 CIN (ANC

<0.5 × 10 9/L) during cycle 1 of CTX. For non-inferiority analysis, a mar-

gin of 0.6 days was dened.

Result: F-627 was non-inferior compared to PEG-FIL for the duration

of Grade 4 CIN in cycle 1 with a mean dierence of 0.0 days (95% CI:

-0.1, 0.1) and a mean duration 0.2 days in both study groups. e inci-

dence of grade 4 CIN in CTX cycle 1 was 11.7% in both study groups.

For subsequent CTX cycles, the incidence of grade 4 CIN was generally

lower than in CTX cycle 1, with a lower incidence noted for pts random-

ized to F-627 compared to PEG-FIL. e incidence and mean duration of

IV antibiotic use and hospitalization due to febrile CIN were comparable

between F-627 and PEG-FIL. e mean time to ANC nadir was slightly

longer with F-627 than with PEG-FIL. F-627 was well tolerated, with a

low incidence of serious AEs and AEs leading to discontinuation, com-

parable to PEG-FIL. ere were 3 drug-unrelated deaths during the study

(F-627:1, PEG-FIL:2).

Discussion: F-627 was non-inferior to PEG-FIL in reducing the duration

of severe CIN following CTX. Further, F-627 was well tolerated with an

overall safety prole comparable to that for PEG-FIL.

Conclusion: F-627 is the rst long-acting G-CSF without PEGylation

and constitutes a safe, eective, and easy to use alternative to current CIN

prophylaxis.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

Poster

100

Complementary and alternative medicine (CAM) supplements

in cancer outpatients: analyses of usage and of interaction

risks with cancer treatment

Clemens Wolf1; Tobias Rachow1; Thomas Ernst1; Andreas Hochhaus1;

Bijan Zomorodbakhsch2; Susan Foller3; Matthias Rengsberger4;

Michael Hartmann5; Jutta Huebner1

1Universitätsklinikum Jena, Klinik für Innere Medizin II, Hämatologie und

Internistische Onkologie, Jena, Deutschland

2Onkologische Kooperation Harz, Goslar, Deutschland

3Universitätsklinikum Jena, Klinik für Urologie, Jena, Deutschland

4Universitätsklinikum Jena, Klinik und Poliklinik für Frauenheilkunde und

Fortpanzungsmedizin, Jena, Deutschland

5Universitätsklinikum Jena, Apotheke des Universitätsklinikums, Jena,

Deutschland

Background: e aim of our study was to analyze the use of comple-

mentary and alternative medicine (CAM) supplements, identify possible

predictors, and analyze and compile potential interactions of CAM sup-

plements with conventional cancer therapy.

Methods: We included outpatient cancer patients treated at a German

university hospital in March or April 2020. Information was obtained

from questionnaires and patient records. CAM–drug interactions were

identied based on literature research for each active ingredient of the

supplements consumed by the patients.

Results: 37.4% of a total of 115 patients consumed CAM supplements.

Potential interactions with conventional cancer treatment were identied

in 51.2% of these patients. All types of CAM supplements were revealed

to be a potential source for interactions: vitamins, minerals, food and

plant extracts and other processed CAM substances. Younger age (< 62

years) (p = 0.020, φc = 0.229) and duration of individual cancer history of

more than 1 year (p = 0.006, φc = 0.264) were associated with increased

likelihood of CAM supplement use. A wide range of dierent CAM sup-

plement interactions were reviewed: eects of antioxidants, cytochrome

(CYP) interactions, and specic agonistic or antagonistic eects with can-

cer treatment.

Discussion: e interaction risks of conventional cancer therapy with

over-the-counter CAM supplements seem to be underestimated.

Conclusion: Supplements without medical indication, as well as over-

doses, should be avoided, especially in cancer patients. To increase patient

safety, physicians should address the risks of interactions in physician–

patient communication, document the use of CAM supplements in

patient records, and check for interactions.

Indication of source: Wolf CPJG et al., Complementary and alternative

medicine (CAM) supplements in cancer outpatients: analyses of usage

and of interaction risks with cancer treatment. J Cancer Res Clin Oncol.

2021 Jul 6. doi: 10.1007/s00432-021-03675-7

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 239

136

Perceived exertion of sensorimotor training in childhood

cancer survivors

Sarah Otten1; Clémentine Bischo2; Aram Prokop3,4,5; Volker Maas3;

Wilhelm Bloch1; Fiona Streckmann2,6; Julia Däggelmann1;

Vanessa Oschwald1

1Institute of Cardiovascular Research and Sports Medicine, German Sport

University Cologne, Department of Molecular and Cellular Sports Medicine,

Cologne, Deutschland

2Department of Sport, Exercise and Health, University of Basel, Basel, Schweiz

3Children’s Hospital Amsterdamer Straße, Cologne, Clinic for Children and Youth

Medicine, Municipal Clinics of Cologne, Department for pediatric hematology/

oncology, Cologne, Deutschland

4Clinic for Children and Youth Medicine, Helios Clinics of Schwerin, Pediatric

Oncology/Hematology, Schwerin, Deutschland

5Medical School Hamburg (MSH), University of Applied Sciences and Medical

University, Hamburg, Deutschland

6Department of Oncology, University Hospital Basel, Basel, Schweiz

Background: To determine the perceived exertion of sensorimotor train-

ing (SMT) in childhood cancer survivors.

Methods: 6 childhood cancer survivors (mixed diagnoses, 7-15 years)

participated in a 4-week SMT intervention. Training was performed 3x/

week (1x supervised, 2x home-based) and consisted of 5 sensorimotor

exercises (5 reps à 10s with 20s rest, 1min rest between exercises). Exercise

intensity was set by combining various positions, surfaces and dual tasks

resulting in overall exercise intensity levels from 3 (low) to 12 (high).

Perceived exertion was determined (1) per RPE-scale (6-20) aer each

training session and (2) per 5-point-likert scale aer the intervention.

Result: Participants mostly chose the overall exercise intensity levels 8 or

9. Mean RPE-value was 11.43 ± 0.91. 2/6 children rated SMT as somewhat

physical demanding and 4/6 chose the answer cannot decide.

Discussion: While most SMT sessions were performed at medium inten-

sity, participants perceived SMT as less intensive. Many children had

diculties in assessing intensity. is may be due to the fact that they

compared their physical exertion during SMT with their experiences of

general strength and endurance exercises. However, in cancer patients

SMT is not applied to promote strength, but primarily to improve for

example balance control and proprioception by inducing neuronal adap-

tion1. us, SMT requires specic training strategies such as short exercise

durations and sucient time for recovery to prevent neuronal fatigue1.

Conclusion: In order to successfully apply SMT in childhood cancer

survivors to achieve improvements in areas such as balance control and

proprioception, children need to be sensitized to SMT, its potential mech-

anisms and especially to its specic training strategies.

Indication of source:

1 Streckmann F, Rittweger J, Bloch W, Baumann FT (2014) Bewegungsempfeh-

lungen bei Chemotherapie-induzierter peripherer Polyneuropathie. Bewe-

gungstherapie und Gesundheitssport 30:179-182

Disclosure Statement: e authors declare no conict of interest.

137

Smoking patterns and motivation to quit in cancer patients:a

cross-sectional study

Frederike Bokemeyer1; Holger Schulz2; Carsten Bokemeyer3,4;

Christiane Bleich2

1Poliklinik und Institut für Medizinische Psychologie, Universitätsklinikum

Hamburg-Eppendorf , Hamburg, Deutschland

2Poliklinik und Institut für Medizinische Psychologie, Universitätsklinikum

Hamburg Eppendorf, Hamburg, Deutschland

3II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie,

Knochenmarktransplantation mit Abteilung für Pneumologie),

Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

4Zentrum für Onkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg,

Deutschland

Background: Continuing to smoke aer cancer can negatively inuence

the course of the disease and the outcome of therapy. Evidence from lit-

erature shows that 40% of patients continue to smoke aer diagnosis.

However, there is still a lack of studies on prevalence, smoking patterns

and motivation to change among cancer patients in Germany and only

few successful international smoking cessation programs exist for these

patients to date. erefore, the aims of this study are: Determination of the

prevalence of smoking cancer patients, smoking patterns, cigarette depen-

dency and the "Stage of Change" concerning the Transtheoretical Model

of Change; identifying sociodemographic, medical, and psychological risk

factors; determination of facilitating and inhibiting factors to take up a

cessation program.

Methods: e study will include more than 1000 cancer patients with

an age of at least 18 and independent of the tumor entity and the phase

of treatment. A questionnaire will be handed out in oncology depart-

ments, outpatient clinics and practices in Hamburg, Germany. e used

instruments are EORTC-QLQ C30 for quality of life, distress thermom-

eter, SSUK for social support, FÄR for the motivation to quit smoking,

FTCD for the cigarette dependency, AUDIT-C for alcohol consumption

and self-developed items for capturing knowledge on the consequences

of smoking as well as qualitative questions regarding own experiences in

prior smoking cessation attempts and needs for future attempts.

Result: Currently more than 846 patients have been recruited. An interim

analysis will be presented.

Discussion: is study is important as there is no comprehensive smok-

ing cessation program for cancer patients in Germany to date. If risk fac-

tors, smoking patterns and motivational aspects of cancer patients are

identied, it is possible to customize smoking cessation programs.

Conclusion: Data on prevalence, smoking behavior, motivational aspects

and potential risk factors will provide a basis for the development of a can-

cer-specic smoking cessation program for German oncological hospitals.

Disclosure Statement: e authors declare no conict of interest.

159

Studydesign of a telemedical training intervention as part

of the study ‘Survivorship Clinic for long-term survivors with

gynecological cancer’

Johanna Porst1; Hannah Woopen2; Jalid Sehouli2; Verena Krell1;

Franziska Greiß1; Stephanie Roll3; Thomas Reinhold3; Stefan N. Willich3;

Maren Keller4; Seyma Boz4; Petra Hühnchen5; Wolfgang Böhmerle5;

Matthias Endres5; Kirsten Wittke6; Carmen Scheibenbogen6;

Adak Pirmorady7; Matthias Rose7; Elisabeth Steinhagen-Thiessen8;

Knut Mai8; Lukas Maurer8; Frank Edelmann9; Reinhold Kreutz10;

Engi Algharably10; Cindy Stoklossa11; Bernd Wolfarth1

1Charité − Universitätsmedizin Berlin, Abteilung für Sportmedizin, Berlin,

Deutschland

2Charité − Universitätsmedizin Berlin, Klinik für Gynäkologie mit Zentrum für

onkologische Chirurgie, Berlin, Deutschland

3Charité − Universitätsmedizin Berlin, Institut für Sozialmedizin, Epidemiologie

und Gesundheitsökonomie, Berlin, Deutschland

4Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie e.V., Berlin,

Deutschland

5Charité − Universitätsmedizin Berlin, Klinik für Neurologie, Berlin, Deutschland

6Charité − Universitätsmedizin Berlin, Institut für Medizinische Immunologie,

Berlin, Deutschland

7Charité − Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt für

Psychosomatik, Berlin, Deutschland

8Charité − Universitätsmedizin Berlin, Medizinische Klinik für Endokrinologie,

Diabetes und Stowechselmedizin, Berlin, Deutschland

9Charité − Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt

Kardiologie, Berlin, Deutschland

10Charité − Universitätsmedizin Berlin, Institut für Klinische Pharmakologie und

Toxikologie, Berlin, Deutschland

11Charité − Universitätsmedizin Berlin, Sozialdienst, Berlin, Deutschland

Background: In the framework of the study ‘Survivorship Clinic for long-

term survivors (LTS) with gynecological cancer’, funded by the German

health care Innovation Fund, one component to promote quality of life

(QoL, primary endpoint) in LTS is the module of sports medicine. A

healthy and active lifestyle can reduce risk factors for cancer recurrence

and therapy-associated long-term side eects. us, physical activity

is essential for tertiary prevention. e goal is to establish an ecient

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts240

training protocol that can be transferred into standard care to promote

physical health for LTS.

Methods: Based on parameters determined by sports medical history and

performance diagnostics, 180 LTS of gynecological cancer receive indi-

vidual training plans over 12 months of intervention. Training protocols

are in accordance with the ACSM exercise guidelines for cancer survivors

(Campbell et al., 2019) and aim for moderate endurance (3x30 min/week)

and strength training (2x/week). Training is telemedically supervised

through an activity tracker, a digital exercise journal and telephone con-

sultation every four weeks. Physical activity is also evaluated every three

months with the IPAQ questionnaire in addition to the activity tracker

evaluation. Every patient’s baseline performance diagnostics results will

be compared with those aer the intervention.

Result: Results will include parameters such as VO2peak, the ventila-

tory thresholds VT1 and VT2, lactate thresholds (individual anaerobic

and 4mmol-threshold) and exercise session adherence aer 12 month of

intervention.

Discussion: Findings of this intervention will provide better knowledge

about the application of sports medical consulting and training manage-

ment through telemedical interventions and the diculties that might

occur in this cohort.

Conclusion: All ndings shall help to establish a sucient protocol for

LTS in the module of sports medicine, with the goal to establish it in stan-

dard care of LTS in gynecological cancer and therefore contribute to a

multidisciplinary approach of promoting QoL.

Disclosure Statement: e authors declare no conict of interest.

169

The impact of whole-body vibration training on the incidence

and the severity of chemotherapy-induced peripheral

neuropathy in breast cancer patients receiving paclitaxel

therapy

Rebecca Dalferth1; Hannah Hebbel1; Nadine Sallach1; Nicolai Maass1;

Anne Letsch2; Thorsten Schmidt2

1Department of Gynecology and Obstetrics, University Medical Center

Schleswig-Holstein (UKSH), Kiel, Deutschland

2University Cancer Center Schleswig-Holstein (UCCSH), University Medical

Center Schleswig-Holstein (UKSH), Kiel, Deutschland

Background: Breast cancer is the most common cancer in women in

Germany and is generally treated with adjuvant chemotherapy, contain-

ing platinum, taxane or vinca alkaloid. e occurrence of chemothera-

py-induced peripheral neuropathy (CIPN) is a very common side eect

of these cytostatic drugs. CIPN can be therapy limiting due to sensorial,

motor, and vegetative impairments. Treatment delay, dose reduction or

discontinuation of the therapy negatively aects the outcome, as well as

the overall survival rate of the patients. In this study we aim to reduce

therapy-induced side eects by application of a supportive sport and

exercise intervention. Positive results will greatly facilitate a more patient-

centered therapy.

Methods: In this prospective randomized controlled trial, 60 breast can-

cer patients are compared regarding the occurrence of CIPN. During the

period of taxane (paclitaxel) administration, two of three study groups

are receiving a twice weekly, one-hour exercise intervention including

strength training or strength training combined with whole-body vibra-

tion (WBV) training. e third group serves as control and does not

receive any training. At xed intervals the patients’ balance and depth

sensitivity are measured, to examine the eect of the exercise intervention

on CIPN-manifestation.

Result: At this point, the study is still in progress. It shows a good feasi-

bility with 35 of 51 patients having completed the nal testing by now. An

overall evaluation of the results will be completed by the time of the con-

gress. e currently available results already show tendencies that exercise

intervention, and particularly WBV training have benecial eects on the

occurrence and the severity of a CIPN.

Discussion: e study is limited by its small size. Furthermore,

patient-questionnaires could not be double-blinded, eventually leading to

a bias in their evaluation.

Conclusion: By mitigating treatment-limiting side eects of CIPN, phys-

ical activity represents a relevant therapeutical option in gynecologic

oncology during paclitaxel therapy.

Disclosure Statement: e authors declare no conict of interest.

172

The impact of whole body vibration on the incidence

and the severity of chemotherapy-induced fatigue and

quality of life in breast carcinoma patients receiving

paclitaxel therapy

Hannah Hebbel1; Rebecca Dalferth1; Nadine Sallach1; Nicolai Maass1;

Anne Letsch2; Thorsten Schmidt2

1Department of Gynecology and Obstetrics, University Medical Center

Schleswig-Holstein (UKSH), Kiel, Deutschland

2University Cancer Center Schleswig-Holstein (UCCSH), University Medical

Center Schleswig-Holstein (UKSH), Kiel, Deutschland

Background: e aim of this prospective randomized controlled study is

to investigate the eectiveness of whole body vibration (WBV) in improv-

ing chemotherapy induced fatigue (CIF) and the quality of life (QOL) in

women with breast cancer receiving paclitaxel.

Methods: 60 breast cancer patients receiving paclitaxel chemotherapy

are randomized into three study groups: strength training (ST), strength

training and whole body vibration (ST+WBV) and control (C). e ST

group absolve a specic strength training two times a week for one hour

while the ST+WBV group has an additional unit on a vibration platform

with a vibrating dumbbell. e control group receives no supervised

exercise training. Primary endpoints CIF, QOL and strength are tested

before the paclitaxel treatment (t1), 6 (t2), 12 (t3) and 18 (t3) weeks aer

the treatment start. Test instruments are the EORTC QLC BR23, C30,

Fatigue/MFI, handmanometry and the chair rising test.

Result: So far, the study shows a good feasibility with 51 patients included

of which 35 completed the program by now. e patient compliance is

very good and the results currently available show tendencies, that WBV

eects CIF and QOL positively. Final results will be available at the time

by the congress in February 2022.

Discussion: CIF and a poor QOL are common reasons for therapy can-

cellation, delay or reduction. If WBV reduces CIF and improves QOL, it

will also have a positive impact on the therapy outcome of those patients.

e studies limitations are its small size and the non-blinded execution

which represents a potential confounder in the analysis of patient-com-

pleted questionnaires.

Conclusion: e preliminary results imply that WBV training benets

women with breast cancer suering from CIF and improves their QOL

so it could become a relevant therapeutic option in gynecologic oncology

during paclitaxel therapy.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 241

180

Patients’ perceptions of an integrated care model in stem

cell transplantation, facilitated by eHealth: Interim results of

a qualitative study, evaluating the implementation process

regarding implementation outcomes and principles of

medical ethics

Linda Wienands1; Julia Krumme2; Lynn Leppla1,3; Alexandra Teynor4;

Sabine Valenta3; Janette Ribaut3; Elisabeth Veronica Mess4;

Sabina De Geest3,5; László Kovács2

1Medical Center University of Freiburg, Faculty of Medicine, Department of

Medicine I, Freiburg im Breisgau, Deutschland

2University of Applied Sciences, Faculty of Liberal Arts and Sciences, Augsburg,

Deutschland

3University of Basel, Institute of Nursing Science, Department Public Health,

Basel, Schweiz

4University of Applied Sciences, Faculty of Computer Science, Augsburg,

Deutschland

5K.U.Leuven, Academic Centre for Nursing and Midwifery, Department of Public

Health and Primary Care, Leuven, Belgien

Background: An integrated care model (ICM) in allogeneic stem cell

transplantation (alloSCT) aims to foster patients’ self-management by a

human (Care Coordinator (CC), educational sessions) and an eHealth

component (remote monitoring system). However, eects of the latter

are associated with ethical issues. For this purpose, we aimed to 1) eval-

uate the implementation process of the ICM regarding implementation

outcomes and medical ethical principles and 2) recommend ethically ori-

ented renements with view to implementation strategies and agile so-

ware development.

Methods: Within a qualitative evaluation study, we conducted N=12

semi-structured interviews with patients post-alloSCT, who experienced

the ICM. Transcripts were analyzed by nursing scientists and ethicists,

using thematic analysis and the framework method. Round tables with

CCs and soware engineers were held to tailor recommendations.

Result: 1) e irritated life and e individual in health care were overar-

ching themes, which explain ndings by contextual and setting factors:

Patients emphasized the importance of CCs as a steady contact in addition

to changing physicians and perceived educational sessions as appropri-

ate and feasible. Feedback was mixed regarding personal benet through

eHealth, which was linked to the need for security due to remote monitor-

ing, technical experience and social support. Ethical issues such as process

transparency, safety issues related to querying symptoms, and exclusions

based on impairment were noted. 2) Ethical recommendations aimed to

provide alternatives to eHealth and create notication features of submit-

ted health data.

Discussion: ICM is a valuable addition to current care, with the human

component as a core element. eHealth is not benecial per se, and despite

renements, it has to be recognized as an adaptable element aer ethical

considerations.

Conclusion: Combining ethics with implementation science and agile

soware development in the evaluation contributes to a responsible use of

eHealth, gaining ground in supportive cancer care.

Disclosure Statement: e authors declare no conict of interest.

197

The role of structural barriers for physical activity behavior

after the cancer diagnosis

Johanna Depenbusch1,2; Joachim Wiskemann3; Alexander Haussmann1;

Angeliki Tsiouris3,4; Laura Schmidt5; Nadine Ungar5; Monika Sieverding5;

Karen Steindorf1

1Deutsches Krebsforschungszentrum (DKFZ) und Nationales Centrum

für Tumorerkrankungen (NCT) Heidelberg, Abteilung Bewegung,

Präventionsforschung und Krebs, Heidelberg, Deutschland

2Universität Heidelberg, Medizinische Fakultät, Heidelberg, Deutschland

3Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg und

Universitätsklinikum Heidelberg, Abteilung Medizinische Onkologie,

Heidelberg, Deutschland

4Universitätsmedizin der Johannes Gutenberg Universität Mainz, Klinik für

Psychosomatische Medizin und Psychotherapie, Mainz, Deutschland

5Universität Heidelberg, Psychologisches Institut, Heidelberg, Deutschland

Background: Dierent barriers have been shown to prevent cancer

patients from pursuing physical activity (PA) aer the diagnosis, but the

role of structural barriers has not been suciently investigated. e cur-

rent study thus aimed to examine determinants of the perception of struc-

tural barriers and its impact on post-diagnosis PA.

Methods: A total of 1299 breast, prostate and colorectal cancer patients

completed a questionnaire on sociodemographic and medical data, pre-

and post-diagnosis PA and perceived PA impediment by seven structural

barriers. Linear regression analyses were used to identify determinants of

the perception of structural barriers. e association between structural

barriers and insucient post-diagnosis PA was evaluated using logistic

regression analyses for the overall sample and for subsamples divided by

pre-diagnosis PA.

Result: Overall, 40-60% of cancer patients felt impeded by structural barri-

ers regarding a lack of disease-adjusted PA oers and support, particularly

those who were younger, not working, had a higher BMI, lower educa-

tion, co-morbidities and reported lacking PA counseling. Individuals who

indicated stronger impediment by structural barriers were signicantly

more likely to be insuciently active post-diagnosis, specically those

with high pre-diagnosis PA.

Discussion: Structural barriers seem to contribute to insucient PA

among people with cancer. Dierences in the perception of barriers with

regard to patient characteristics are relevant for a more specic targeting

of interventions. e association between structural barriers and post-

diagnosis PA further points out the need for tailored PA programs as well

as patient education and support.

Conclusion: Our results highlight important target points for the devel-

opment and implementation of disease-adjusted interventions that might

help cancer patients to overcome structural barriers and improve PA, e.g.

as established in the network OnkoAktiv1.

1 www.netzwerk-onkoaktiv.de

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts242

229

High need for information regarding physical activity in

patients with myeloproliferative neoplasms - results of a

multicenter questionnaire study (OSHO-#97)

Sabine Felser1; Christina Große-Thie1; Christa Unger1; Philipp Le Coutre2;

Susann Schulze3,4; Lars-Olof Muegge5; Julia Grün1; Christian Junghanß1;

East German Study Group of Hematology and Oncology (Osho)6

1Rostock University Medical Center, Department of Medicine Clinic III,

Hematology, Oncology, Palliative Medicine, Rostock, Deutschland

2Campus Virchow-Klinikum, Charité, Medical Clinic with emphasis on

Hematology and Oncology, Berlin, Deutschland

3Krukenberg Cancer Center Halle (Saale), University Hospital Halle,

Halle (Saale), Deutschland

4Carl-von-Basedow-Klinikum, Department of Medicine Clinic II,

Hematology, Oncology, Palliative Medicine, Merseburg, Deutschland

5Heinrich Braun Klinikum Zwickau, Department of Internal Medicine III,

Zwickau, Deutschland

6Ostdeutsche Studiengruppe Hämatologie und Onkologie e. V.,

Leipzig, Deutschland

Background: Cancer and its treatment oen lead to a decrease in physi-

cal and mental performance. To address this fact special exercise recom-

mendations can be given. ese recommendations are commonly derived

from solid tumor patients (pts) studies. In order to minimize the risk of

exercise induced adverse events, the given recommendations are usually

oriented on the current pts side-eects. Pts with myeloproliferative neo-

plasms (MPN) suer frequently from splenomegaly accompanied by loss

of appetite and weight. Further, these patients are oen anticoagulated due

an increased thrombotic event risk. Specic recommendations addressing

these facts are not available. Aim of the study is to characterize MPN spe-

cic symptoms, side eects and anxiety in order to allow the development

of MPN tailored exercise recommendations. In order to increase pts com-

mitment our study also considers patient specic exercise preferences.

Methods: Ongoing MPN pts one-time multicenter anonymous survey

including: (1) demographic data, (2) disease and treatment data, (3) cur-

rent well-being, symptoms, and side eects, and (4) exercise behavior,

information level and preferences1.

Result: A total of 706 questionnaires were analysed. A high rate of dier-

ent symptoms as moderate to high fatigue (54%) and moderate to severe

bone/muscle pain (39%) were observed. Two hundred and three pts (30%)

had an enlarged spleen and 20% had an increased bleeding tendency with

hemorrhage at the time of the survey. More than 40% of pts feel inade-

quately informed about the importance and benets of physical activity,

and 62% would like more information.

Conclusion: MPN pts have a high demand for information regarding the

importance and eects of physical activity.

Indication of source:

1 DRKS-ID: DRKS00023698

Disclosure Statement: e authors declare the following:

Speaker Honorare von Novartis, BMS, Pzer und Incyte

298

Seminar “Patient Empowerment” as a support for

chemotherapy treated patients with breast cancer and

gynecological malignancies - a pilot project of the LMU

Women’s Hospital Munich

Hannah Holländer1; Petra Ortner2; Alexander König1; Nicole Erickson3;

Kerstin Hermelink1; Tom Degenhardt1; Sven Mahner1; Nadia Harbeck1;

Rachel Würstlein1

1Klinikum der Universität München, Klinik und Poliklinik für Frauenheilkunde

und Geburtshilfe, München, Deutschland

2POMME-med GmbH, München, Deutschland

3Klinikum der Universität München, Comprehensive Cancer Center (CCC Munich

LMU), München, Deutschland

Background: Cancer patients may substantially benet from supportive

oers. e seminar "Patient Empowerment" was designed to familiarize

patients and their caregivers with supportive measures focusing on under-

standing of disease, therapy and side eect management.

Methods: e seminar consists of two two-hour parts at intervals of one

month and includes a general introduction with time for questions, talks

and discussions with specialists, supplemented by information materials

on the topics nutrition, exercise, psychooncology and complementary

medicine.

Four seminar groups consisting of patients with breast cancer or gyne-

cological malignancy prior to the start of chemotherapy and, optionally, a

caregiver were formed. e evaluation is based on a self-developed ques-

tionnaire as well as validated questionnaires on disease-related quality of

life (QoL) (EORTC-QLQ-C30, BR23, CX24, OV28), anxiety and depres-

sion symptoms (HADS-D) at four time points: before the seminar, aer 4,

9 and 12 weeks. A control group of comparable patients without seminar

participation was evaluated at baseline and aer 12 weeks.

Result: Between October 2020 and May 2021, 19 patients and 9 compan-

ions participated in the seminar. e control group included 20 patients.

Patients and caregivers were highly satised with the seminar and stated

to recommend it (96,4% agreement on both points).

e QoL deteriorated signicantly in the control group and only

slightly in the intervention group (control: w0=67,6; w12=61,7; interven-

tion: w0=60,8; w12=60,7).

A signicant increase could be found in the reported knowledge about

side eects in the intervention group.

Discussion: e seminar was successful as all participants gave positive

feedback and reported increase in knowledge. ere was also a trend in

improved maintenance of QoL which would need to be conrmed by a

larger number of participants.

Conclusion: e contents of the seminar will be made available virtually

to all patients of the oncological day clinic to supplement the therapy with

supportive oers in the best possible way.

Disclosure Statement: e authors declare no conict of interest.

321

Ecacy of face-to-face behavior change counseling

interventions on physical activity behavior in cancer

survivors – a systematic review and meta-analysis

Corinna Meyer-Schwickerath1,2; Christina Morawietz3; Freerk Baumann4;

Gerhard Huber1; Joachim Wiskemann2

1Institut für Sport und Sportwissenschaft Heidelberg, Universität Heidelberg,

Heidelberg, Deutschland

2Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

3Institut für Sport und Sportwissenschaft, Universität Duisburg-Essen, Duisburg,

Deutschland

4Klinik für Innere Medizin, Uniklink Köln, Köln, Deutschland

Background: is systematic review and meta-analysis of randomized

controlled trials determines the ecacy of face-to-face behavior change

counseling (BCC) interventions on physical activity (PA) behavior in

adult cancer survivors at least pre-and immediately post-intervention

compared to usual care. Additionally, this review aims to answer the ques-

tion which behavior change techniques (BCTs) are most eective.

Methods: A structured search of the databases Medline, OTseeker, PEDro,

the Cochrane Library, and article reference lists was conducted. All tri-

als were critically appraised for methodological quality using the PEDro

scale. e BCC interventions were coded using the BCT Taxonomy (v1).

Random eect meta-analysis explored between group dierences in

PA behavior post intervention. Standardized mean dierences (SMD)

describe eect sizes.

Result: Fourteen studies were included, 12 eect sizes within 11 trials

were pooled in meta-analysis. e SMD between groups favored the

intervention group with a small eect (SMD 0.22; 95% CI 0.11, 0.33;

p < 0.0001). e BCTs “graded tasks”, “self-monitoring of behavior”,

“action planning” and “habit reversal” were more frequently coded in

more ecacious interventions.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 243

Discussion: Although small dierences are evident, included trials pre-

sented with a broad variety of study components, and characteristics,

which limits the interpretation of eective components.

• e behavior change techniques “Graded tasks”, “Action planning”,

“Habit reversal”, and “Credible Source” were used in the trials with a

positive eect, but not in the ineective ones.

Conclusion: BCC interventions are eective in increasing PA behavior in

cancer survivors. Further research is needed providing details of delity

assessment and structuring the intervention description by using a BCT

taxonomy. Health care professionals should consider our results while

awaiting further trial evaluation.

Disclosure Statement: e authors declare no conict of interest.

547

Clinical recommendations for treating Chemotherapy-

Induced Peripheral Neuropathy (CIPN) based on expert

opinions and ndings from a systematic scoping review

Nadja Klafke1; Jasmin Bossert1; Birgit Kröger2; Petra Neuberger3;

Ute Heyder4; Monika Layer5; Marcela Winkler6; Christel Idler6;

Elke Kaschdailewitsch7; Rolf Heine8; Heike John9; Tatjana Zielke9;

Beeke Schmeling9; Sosamma Joy10; Isabelle Mertens10; Claudia Witt11;

Diana Steinmann9; Petra Voiss10; Regina Stolz2

1Abteilung Allgemeinmedizin und Versorgungsforschung , Universitätsklinikum

Heidelberg, Heidelberg, Deutschland

2Institut für Allgemeinmedizin und Interprofessionelle Versorgung,

Universitätsklinikum Tübingen, Tübingen, Deutschland

3Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg,

Heidelberg, Deutschland

4Onkologie / Chemo Ambulanz Frauenklinik / Kardiologie / Neurologie,

Städtisches Klinikum Karlsruhe, Karlsruhe, Deutschland

5Zentrum für Integrative Onkologie, Kantonsspital St. Gallen, St. Gallen, Schweiz

6Naturheilkunde und Integrative Medizin, Robert-Bosch-Krankenhaus,

Stuttgart, Deutschland

7Zentrum für Integrative Onkologie, Die Filderklinik, Filderstadt, Deutschland

8Netzwerk anthroposophische Pege in Deutschland, Akademie für

Pegeberufe an der Filderklinik, Filderstadt, Deutschland

9Klinik für Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule

Hannover, Hannover, Deutschland

10Klinik für Naturheilkunde und Integrative Medizin, Integrative Onkologie,

Evang. Kliniken Essen-Mitte, Essen, Deutschland

11Institut für komplementäre und Integrative Medizin, Universitätsspital Zürich,

Zürich, Schweiz

Purpose: CIPN is a frequent burden experienced by cancer patients.

Symptoms of CIPN are dicult to treat the conventional way, and patients

highly demand complementary therapies. e purpose of this study was

to provide evidence-based treatment options for the supportive treatment

of CIPN.

Methods: e research question developed from an expert symposium on

“supportive management for neuropathy” in 2018 with participants from

Germany and Switzerland experienced in the eld of integrative oncology,

where a consensus process was conducted for presenting interventions for

CIPN treatment management. e review (registered at PROSPERO 2020,

CRD 42020165851) followed the PRISMA-ScR Checklist and the JBI rec-

ommendations for scoping reviews. e literature search was conducted

in the databases of MEDLINE, Cochrane Central, CINAHL, PsycINFO,

and PEDro. All included studies were assessed with CASP.

Results: In total, 17 naturopathic interventions (13 external applications,

hypothermia/cryotherapy, hydrotherapy, and tactile stimulation) were

consented and recommended by the 16 experts. 72 studies with mainly

good study quality, representing 16 complementary treatment options,

were included in the review. ere is external evidence that manipula-

tive therapies (including massage, reexology, therapeutic touch, rhyth-

mical embrocations), movement and mind-body therapies, acupuncture/

acupressure, TENS/Scambler therapy as well as nutritional therapies are

eective complementary treatment options for CIPN.

Discussion: Applications from classical natural medicine seem to pro-

duce positive eects in complex CIPN symptomatology. Future studies

should pay even more attention to methodologically careful study design.

Conclusions: ere are non-pharmacological treatment options available

for the supportive treatment of CIPN and healthcare professionals need to

be educated about them.

Disclosure Statement: e authors declare no conict of interest.

575

Preliminary experiences of a 6-week bicycle ergometer

training for children and adolescents during hospitalization

for acute cancer therapy: Two case studies

Vivien Lösse1; Meinolf Siepermann1; Vanessa Oschwald2; Volker Maas1;

Wilhelm Bloch2; Julia Däggelmann2

1Children’s Hospital Amsterdamer Straße, Cologne, Clinic for Children and Youth

Medicine, Municipal Clinics of Cologne, Department for pediatric hematology/

oncology, Cologne, Deutschland

2Institute of Cardiovascular Research and Sports Medicine, German Sport

University Cologne, Department of Molecular and Cellular Sports Medicine,

Cologne, Deutschland

Purpose To describe preliminarily experiences of bicycle ergometer train-

ing for children and adolescents during hospitalization for acute cancer

therapy.

Methods A supervised 6-week bicycle ergometer training (3x/week) was

oered to pediatric cancer patients during hospitalization for acute can-

cer treatment. Training protocol comprised continuous cycling for at least

10min (max. 40min) at constant speed (cadence: 60-80rpm); workload

was initially set at 0watt and progressively increased if the patient suc-

ceeded to cycle 10 continuous minutes without interruption. Training

attendance, reasons for non-attendance, training duration and achieved

workload were documented.

Results Patient A (female, 10 years, lymphoma) attended 9/18 sessions.

Reasons for non-attendance were: not hospitalized on the day of training

(8x), medical issues (1x). Training duration ranged from 5-16min. Only

cycling without resistance was possible. Patient B (female, 18 years, lym-

phoma) participated in 9/18 sessions. Reasons for non-attendance were:

not hospitalized on the day of training (5x), medical issues (4x). Training

duration ranged from 10-35min. Workload was increased in one session

up to 25watt.

Discussion Both patients could participate in the intervention. However,

attendance rate was relatively low, as the patients were oen not hospital-

ized on the day of training. If admitted, patients could participate in most

of the oered sessions for at least a few minutes. Workload remained low.

Conclusions Low-intensity bicycle ergometer training seems feasible

during hospitalization for acute pediatric cancer therapy. To improve

attendance and overall exercise time, an individualized and exibly

scheduled training (e.g. even twice per day) needs to be oered. Due to

uctuating patient abilities and low exercise capacity, training should be

supervised.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts244

614

Hurdle race for oncological exercise providers: Barriers and

facilitators for the implementation of oncological exercise

programs in the network OnkoAktiv

Annelie Voland1,2; Annette Lohmann1,2; Maximilian Köppel1,2;

Lena Ansmann3; Joachim Wiskemann1,2

1Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

2Universitätsklinikum Heidelberg, Heidelberg, Deutschland

3Carl von Ossietzky Universität Oldenburg, Department für

Versorgungsforschung, Abteilung Organisationsbezogene

Versorgungsforschung, Oldenburg, Deutschland

Background: A great body of scientic evidence supports the positive

impact of exercise on cancer patients and survivors. However, oncological

exercise provision in Germany is highly heterogeneous and incomplete

in implementation. e network OnkoAktiv (OA) certies exercise insti-

tutions based on quality indicators and connects them with cancer care

providers to oer high quality oncological exercise programs.

Objective: is work evaluates barriers and facilitators for the implemen-

tation of cancer-specic exercise programs within OA.

Methods: is evaluation is executed in a sequential mixed methods

design. Eight qualitative, semi-structured interviews with leading exercise

therapists were conducted based on the CFIR framework. Aer qualita-

tive analysis, a quantitative, cross-sectional questionnaire was developed

based on qualitative results and literature research. e nal survey will

be send out to all certied OA exercise institutions (n=89) via email in

09/2021.

First results: e qualitative analysis shows facilitators in the inner set-

ting of the interviewed institutions such as existing institutional resources

(n=79), e.g. training equipment, time capacities, qualied sta and reg-

ular team meetings. Further, interviewee showed high personal interest

and intrinsic motivation in exercise oncology (n=26) and they observed

a unique selling point of oncological programs in their regions (n=11). In

the outer setting, cooperation with medical professionals (n=27) as well as

professional marketing (n=35) seem to be highly important for successful

implementation. Barriers are indicated in the outer setting, e.g. lack of

cooperation with oncologists and clinics (n=29) and missing exercise-re-

lated guidance and allocations of patients from practitioners (n=21).

Further, clearing costs with health insurances are describes as incomplete

(n=12).

Expectations: We expect detailed information about barriers and facil-

itators regarding the implementation of oncological exercise programs

within OA. Final results will be presented in 02/2022.

Disclosure Statement: e authors declare no conict of interest.

615

Introduction of digital aftercare in oncology

Ivonne Rudolph1; Bettine Bilsing1

1Waldburg- Zeil Kliniken, Rehabilitationsklinik Bad Salzelmen, Schönebeck,

Deutschland

Background: e time- and location-independent training is an advan-

tage of digital aercare and thus a promising addition to the previous

rehabilitation programs on site. A continuous training aer completion

of the rehabilitation is imperative (1, 2). is can be ensured by the dig-

ital aercare. e Rehabilitation Clinic Bad Salzelmen is carrying out a

pilot study concerning oncological digital aercare from July to December

2021. e aim is to familiarize Mamma-Ca patients in rehabilitation with

the possibilities of digital therapy. ereby an awareness of the advantages

that digital aercare can provide shall be created.

Methods: As part of the pilot study, the technical requirements are

explained to the participants in an information event. Following digital

training units are carried out together. Aer completing the rehabilitation,

the women can start training in digital aercare immediately. Participants

receive the individual training plan online and can talk to their therapist

at any time. e focus of the exercises is strengthening and exibility of

shoulders and arms. e primary study goals are evaluating the acceptance

of digital therapy forms and check the participants compliance regarding

digital aercare. Due to the duration of the pilot study, the nal results, the

discussion and the conclusion will be presented at the DKK 2022

Indication of source

1 Jung, A., Y., Behrens, S., Schmidt, M., oene, K., Obi, N., Hüsing,A.,

Benner, A., Steindorf, K., Chang-Claude, J.: Pre- to postdiagnosis lei-

sure-time physical activity and prognosis in postmenopausal breast

cancer survivors. Breast Cancer Research 2019.

2 Buart, L.M., Galvão, D.A., Brug, J., Chinapaw, M. J. M., Newton,

R.U.: Evidence-based physical activity guidelines for cancer survivors:

current guidelines, knowledge gaps and future research directions.

Cancer Treat Rev .2014 Mar 40 (2):327-40.

Disclosure Statement: e authors declare no conict of interest.

621

A Bavarian health care inventory on supportive cancer care

provision (BEQUEST Study): use case cancer associated

thrombosis (CAT):

Vanessa Kratzer1; Frank Ng2; Rupert Bauersachs3; Roman Gerlach4;

Roland Jucknewitz5; Christoph Kalka6; Robert Klamroth7;

Ulrich Mansmann1; Helmut Ostermann8; Jutta Schimmelpfennig9;

Martin Tauscher4; Mandy Schulz2

1Institut für medizinische Informationsverarbeitung, Biometrie und

Epidemiologie, Medizinische Fakultät, München, Deutschland

2Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik

Deutschland, Berlin, Deutschland

3Cardioangiologisches Centrum Bethanien (CCB) Gefäß Centrum, Frankfurt,

Deutschland

4Kassenärztliche Vereinigung Bayerns (KVB), München, Deutschland

5AOK Bayern - Die Gesundheitskasse, Regensburg, Deutschland

6Zentrum für Gefässmedizin, Baden, Schweiz

7Klinik für Innere Medizin – Angiologie und Hämostaseologie, Vivantes Klinikum

im Friedrichshain, Berlin, Deutschland

8LMU Klinikum der Universität München - Campus Großhadern, München,

Deutschland

9“Aktionsbündnis Thrombose“ der DGA, DGP, GTH,DGG, Deutschen Gefässliga,

Berlin, Deutschland

Background: To provide the best possible and sustainable health care

for patients (pts) with cancer in Bavaria information on epidemiology,

treatment patterns, patient journeys and outcomes are key. Aim of the

BEQUEST (Bedarfsgerechte und Qualitätsorientierte Versorgung von

Patienten mit Venöser rombose in Bayern) study, is the provision of

aforementioned information by a mixed methods design using dierent

data sources for the use case of CAT pts.

Methods: e present study is based on the Bavarian outpatient claims

data of the panel doctors services according to §295 SGB V to determine

epidemiology, diagnostic and treatment patterns, outcomes and settings.

Inclusion criteria is age > 18years with an active cancer (ICD-10-GM: C.

00-99) diagnosis and an incident DVT (I.80).

Result: In Bavaria 38.390 statutory health insured pts (6% of cancer pts)

suered from an incident DVT between 2016-2018. More than half (55.1

%) live in rural areas. Mean age is 69.7 years (median 72.3), 59 % are

female, average Elixhauser comorbidity index score is 6.4. Main underly-

ing diseases are malignant neoplasms of skin, without specic localization,

of gastrointestinal tract, and of breast. On average, 22.4% pts experience a

disorder of veins e.g. post thrombotic syndrome (I.87), 9.1 % suer from

a pulmonary embolism (I.26) within 15 months aer DVT. In large cities

a heterogeneous group of specialists (Vascular surgery, Angiology etc.) is

involved in patient care compared to sparsely populated districts, where

care is concentrated on general practitioners.

Discussion and Conclusion: e results show a signicant number of pts,

mainly elderly, with CAT. At least every h pt suers from a subsequent

event. For a comprehensive analysis on access to equivalent health care,

BEQUEST will focus in further analyses on outcomes and their correlation

with the involved specialist groups and structural regions. Additionally

the physicians and patient perspective is incorporated by two surveys.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 245

630

Target Groups for Exercise Counseling in Multiple Myeloma

Patients: A Latent Prole Analysis

Rea Kühl1; Maximilian Köppel1; Hartmut Goldschmidt2; Joachim

Wiskemann1

1Nationales Centrum für Tumorerkrankungen – NCT, Medizinische Onkologie,

AG Onkologische Sport- und Bewegungstherapie, Heidelberg, Deutschland

2Department Innere Medizin/Klinik für Hämatologie, Onkologie und

Rheumatologie, Myelomzentrum Heideberg, Heidelberg, Deutschland

Background: e safety and ecacy of exercise for cancer patients all

along the trajectory is supported by a large body of evidence. In order to

ensure maximum eects for the individual patient it is important to take

the symptoms, contraindications and competences of exercise into con-

sideration. is is crucial when dealing with complex patients, like those

with multiple myeloma.

Methods: We conducted a survey including 126 patients with multiple

myeloma and assessed their health related quality of life, symptoms such

as pain and fatigue, and physical activity associated health competence

(PAHCO). e resulting data were analyzed via latent prole analysis

(LPA) to identify homogeneous clusters of patients in regards to their

symptoms and PAHCO, which can be utilized as basis for exercise coun-

seling in a very heterogenous population of myeloma patients.

Result: In both analyses the solution involving four distinct proles

showed the best model t. Furthermore, all proles showed high discrim-

inatory power (> 93% probability of prole aliation given the data).

ese proles can be labeled with patients having high, slightly elevated

and decreased as well as low symptom severity for the rst LPA and

patients with high, moderate, moderate-to-low and very low PAHCO. e

prole validation showed high agreement with our hypothesis.

Discussion: e results show that while a proportion of patients need spe-

cic motivational and educational aspects for their exercise counseling,

others already display a high competence in this regard. A proportion of

patients need a very target-specic approach in exercise therapy to reduce

their symptoms while others benet most from a more generic approach

to maintain their well being.

Conclusion: e identied proles allow a personalized approach for the

eectiveness of exercise counseling for cancer patients and promotes a

more ecient allocation of personnel resources.

Disclosure Statement: e authors declare no conict of interest.

647

Exercise in the context of cardiotoxicity in cancer

patients – current evidence and future directions

Nora Zoth1; Annika Tomanek1; Miriam Götte2,3; Uta Dirksen2,3;

Freerk T. Baumann1

1Uniklinik Köln, Klinik für Innere Medizin I, Onkologische Bewegungsmedizin,

Köln, Deutschland

2Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Klinik für

Kinderheilkunde 3, Essen, Deutschland

3Deutsches Konsortium für Translationale Krebsforschung, Standort Essen,

Deutschland

Background: Cardiovascular diseases are one of the leading causes of

non-cancer-related mortality in cancer survivors. us, the need for pre-

ventive strategies as well as early and sensitive predictors of cardiotoxicity

is rising.

Methods: Publications on the eects of exercise in the prevention of

cancer treatment-induced cardiac damages have been overviewed.

Additionally, data regarding cardiovascular function and cardiological

data were analysed.

Result: Pre-clinical research indicates that exercise might be a promising

strategy to prevent chemotherapy-induced cardiac damages. By the time

only less is known about the eects and molecular mechanisms. In clin-

ical research, exercise did neither lead to a signicant impact on the le

ventricular ejection fraction (LVEF) or le ventricular strain (LV strain)

nor on biomarkers as Troponin and Nt-pro BNP. Positive eects, in con-

trast, have been shown on general risk factors for cardiac sequelae such as

bodyweight, hypertension or cardiorespiratory tness. Current research

suggests that Vo2peak is a promising sensitive method to detect early signs

of heart failure.

Discussion: Reductions in LVEF occur late in the course of myocardial

dysfunction aer cardiac damage has already occurred. Cardiorespiratory

tness (VO2peak) is strongly associated with all-cause mortality and

especially cardiac dysfunction and seems to be a promising tool to detect

cardiac damage.

Conclusion: Although evidence is very limited, exercise seems to have

a great potential regarding cardio-protective mechanisms. In particular,

cardiorespiratory function might be an early and sensitive predictor of

cardiotoxicity. Still, the linkage between exercise and cardiotoxicity in

cancer patients remains ambiguous. erefore, as sites of the National

Center for Tumor Diseases (NCT), the University Hospitals Cologne and

Essen, plan to create a multi-centric and multi-disciplinary research proj-

ect, including observational as well as interventional studies.

Disclosure Statement: e authors declare no conict of interest.

659

Eects of a 4-week online-based dance intervention

for childhood cancer survivors on selected motor abilities

Theresa Walz1; Louisa Jung1; Stefan Balzer2; Volker Maas2;

Vanessa Oschwald1; Wilhelm Bloch1; Julia Däggelmann1

1Institute of Cardiovascular Research and Sports Medicine, German Sport

University Cologne, Department of Molecular and Cellular Sports Medicine,

Cologne, Deutschland

2Children’s Hospital Amsterdamer Straße, Cologne, Clinic for Children and Youth

Medicine, Municipal Clinics of Cologne, Department for pediatric hematology/

oncology, Cologne, Deutschland

Purpose To compare the development of selected motor abilities of

childhood cancer survivors with that of healthy peers during an online-

based dance intervention.

Methods 10 children (overall group, age 7-20) including 6 childhood

cancer survivors (patient group, mixed diagnoses) and 4 healthy children

(comparison group) participated in a 4-week online-based dance inter-

vention. Training (2x/week for 30 min via Zoom) comprised a warm-up,

dance choreographies (main part) and stretching exercises. Static balance

(one-leg stand), lower limb strength (5 times sit-to-stand-test), coordi-

nation under time pressure (sideway jumps) and exibility of the ischi-

ocrural musculature (forward bend) were investigated before and aer the

intervention.

Results Forward bend in the patient group and in the overall group and

sideway jumps in the overall group were signicantly improved. Positive

trends were found for sideway jumps in the patient group and one-leg

stand in the overall group.

Discussion e online-based dance intervention seems to have a positive

impact on the motor abilities of participants, that may be due to charac-

teristics of dancing like e.g. changes of direction and stretching exercises.

Pediatric cancer survivors may especially benet regarding exibility and

coordination. As children with cancer oen suer from restricted motor

abilities caused by medical therapy and associated inactivity1, this might

be a reason for the major improvements in this group.

Conclusions In childhood cancer survivors dancing may be a promising

exercise modality to improve restricted motor abilities that are prerequi-

site for being active. Dancing can even be applied online-based.

References:

1 Söntgerath, R. & Eckert, K. (2015). Impairments of Lower Extremity

Muscle Strength and Balance in Childhood Cancer Patients and Survivors:

A Systematic Review. Pediatric hematology and oncology, 32 (8), 585-612

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts246

673

Movement and Exercise Guideline in Pediatric Oncology – an

AWMF-S2k guideline of the Network ActiveOncoKids

Gabriele Gauß1,2; Sabine Kesting3,4; Oliver Basu2,5; Freerk T. Baumann6;

Joachim Boos7; Ursula Creutzig8; Uta Dirksen2,9; Sarah Döring10;

Katharina Eckert11; Robert Erschig12; Anna-Maria Goebel13; Pablo Hernáiz

Driever13; Ingo Menrath14; Aram Prokop15; Dominik Schneider16;

Jannos Siaplaouras17; Sandra Stössel18; Hannah Stalf19; Arne Streitbürger9;

Andreas Wiener20; Joachim Wiskemann21; Torge Wittke22; Miriam Götte2,5

1Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin,

Kinderheilkunde 3, Essen, Deutschland

2Deutsches Konsortium für Translationale Krebsforschung, Standort Essen,

Deutschland

3Technische Universität München, Fakultät für Sport- und

Gesundheitswissenschaften, Lehrstuhl für Präventive Pädiatrie, München,

Deutschland

4Klinikum Schwabing, Klinik und Poliklinik für Kinder- und Jugendmedizin,

Kinderklinik München Schwabing, München, Deutschland

5Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Kinderheilkunde 3,

Essen, Deutschland

6Uniklinik Köln, Klinik für Innere Medizin I, Köln, Deutschland

7Westfälische Wilhelms-Universität Münster, Münster, Deutschland

8Medizinische Hochschule Hannover, Abteilung für Pädiatrische Hämatologie

und Onkologie, Hannover, Deutschland

9 Universitätsklinikum Essen, Klinik für Tumororthopädie und Sarkomchirurgie,

Essen, Deutschland

10Uniklinikum Münster, Physiotherapie Pädiatrie, Münster, Deutschland

11IST-Hochschule für Management, Düsseldorf, Deutschland

12Rehaklinik Katharinenhöhe, Schönwald, Deutschland

13Charité - Universitätsmedizin Berlin, Pädiatrische Klinik mit Schwerpunkt

Onkologie und Hämatologie, Berlin, Deutschland

14Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Kinder-

und Jugendmedizin, Lübeck, Deutschland

15Helios Kliniken Schwerin, Kinder- und Jugendmedizin, Schwerin, Deutschland

16Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin, Dortmund,

Deutschland

17Praxis am Herz-Jesu-Krankenhaus, Kinderkardiologie, Fulda, Deutschland

18Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Mainz,

Deutschland

19Universitätsklinikum Frankfurt am Main, Pädiatrische Onkologie, Hämatologie

und Hämaostaseologie, Frankfurt a.M., Deutschland

20Universitätsklinikum Essen, Westdeutsches Protonenzentrum, Essen,

Deutschland

21Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen

(NCT) Heidelberg, Abteilung Medizinische Onkologie, Heidelberg, Deutschland

22Universitätsklinikum Halle (Saale), Krukenberg Krebszentrum Halle, Halle

(Saale), Deutschland

Background: Pediatric cancer leads to reduced exercise participation and

only few patients comply with the national recommendations on physical

activity. is physically inactive behavior increases not only the physical

and psychological adverse eects of therapy, but also the incidence and

extent of sequelae. Currently, there is neither nationwide coverage nor

uniform level of knowledge regarding exercise promotion. e objective

of the guideline is to enable qualied exercise interventions through stan-

dardized procedures in addition to regular physiotherapy.

Methods: is guideline addresses the interdisciplinary treatment team

(pediatric oncologists, tumor orthopedists, neuropediatricians, psycho-

social service, physiotherapists, sports physicians, sports scientists, etc.)

as well as decision-makers in acute hospitals and health insurance. We

followed the requirements of the Association of the Scientic Medical

Societies in Germany (AWMF). Contents were based on practical experi-

ence of experts, patient advocates, and scientic ndings.

Result: e guideline consists of 11 recommendations. Recommendations

1 to 4 declare the relevance of implementing exercise promotion and exer-

cise interventions forming the basis of the guideline. Recommendations

5 to 11 address general framework conditions for implementation, the

design of exercise programs, and options to overcome barriers to move.

Discussion: is guideline summarizes existing structures and evidence

in the context of movement and exercise in pediatric oncology. It takes

into consideration the varying needs and characteristics of children and

adolescents as well as existing national and international experience in

this eld. We identied relevant research gaps regarding targeted exercise

interventions that hampered the development of a S3 guideline.

Conclusion: is guideline provides support in implementing exercise in

pediatric oncology.

Disclosure Statement: e authors declare no conict of interest.

682

Same plant- same indication? Comparing plants used in

Traditional European Medicine and Kampo medicine

Sören Klaus Büntzel1, Maria-Louisa Ritschel1, Judith Büntzel2

1Otto von Guericke Universität Magedeburg, Universitätsklinikum Magdeburg,

Magdeburg, Deutschland

2Georg-August-Universität, Universitätsmedizin Göttingen, Klinik für

Hämatologie und Onkologie, Göttingen, Deutschland

Background: Already Hildegard of Bingen described medical plants like

Alpinia ocinarum, that are part of the traditional Japanese Kampo med-

icine. Deviating from this historically known common feature of TEM

and Kampo medicine, we posed the question how much the ocially

mandated canons of German TEM plants and Kampo plants overlap.

Methods: Medicinal plants ocially mandated by the Bundesministerium

für Arzneimittel und Medizinprodukte (BfArM) and 103 ocial Kampo

formulas were searched. A matrix was generated, showing if a medical

plant was used in a certain formula grouping plants of the same fam-

ily together. VENN diagrams were used to nd common TEM/Kampo

plants. Indications of German and Kampo plants were compared using

primary component analysis and heat-map cluster analysis.

Result: Our research yielded 14 plants that are both used in TEM and

Kampo medicine: Alpinia ocinarum, Citrus x aurantium, Foeniculum

vulgare, Angelica spp., Asparagus spp., Cinnamomum spp., Gentiana

spp., Glycyrrhiza spp., Mentha spp., Panax ginseng, Plantago spp., Rheum

spp., Syzygium aromaticum and Zingiber ocinale. While certain plants

share common indications like Panax gingseng or Foeniculum vulgare,

we observed frapping dierences regarding Mentha spp., Angelica spp. or

Zingiber ocinale in primary component analysis.

Discussion: As Kampo medicine garners more and more interest in

Western Europe, we need to assess what dierences and common features

these two traditional medical systems share. We are the rst to compare

medical plants ocially mandated by the BfArM with plants used in 103

Kampo formulas, identifying 14 common plants that, however, dier

sometimes in their indications.

Conclusion: TEM and Kampo medicine share common plants, indica-

tions for using these plants vary between medical systems. Western med-

icine oncologists should be aware of these dierences.

Disclosure Statement: e authors declare no conict of interest.

686

“I do not hear you!” – deaf and hard hearing cancer patients

report their communication experiences

Maximilian Keck1; Jan Münstermann1; Jutta Hübner1; Jens Büntzel2

1Universitätsklinikum Jena, Klinik für Hämatologie und internistische Onkologie,

Jena, Deutschland

2Südharz-Klinikum Nordhausen, Klinik für HNO-Erkrankungen, Nordhausen,

Deutschland

Objective: Hard of hearing and deafness have an high impact on com-

munication between cancer patients and their oncologists. What is the

patient’s perspective on this problem?

Material and Methods: Together with bad hearing patients we developed

a questionnaire combining ve complexes: WHO-5-wellbeing question-

naire (5 items) Abbreviated Prole of Hearing Aid Benet (APHAB) as

established self estimation of hearing function (24 items), patient’s expe-

riences in direct conservations with their physicians (15 items), patient’s

diculties in talks (9 items), and patient’s wishs for further support in the

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 247

eld (7 items). According to APHAB scores we analyzed the experiences,

diculties and support wishes as well as life satisfaction of cancer patients.

Results: We included 104 hard hearing cancer survivors (median age 76.5

a, range 32-90). 56/104 (53.8%) had no hearing aid, 43/48 (89.5%) patients

with hearing aid report benet. Despite hearing aids APHAB scores of

>40% were seen in 46/104 patients (less hearing group 1), compared to 51

patients with APHAB scores <40% (better hearing group 2). We registered

signicant dierences in diculties to talk (20.73 +/- 6.00 vs. 14.93 +/-

6.69, p<0.001), need for further support (13.79 +/- 5.27 vs. 11.21 +/- 4.77,

p=0.02), and well being (12.35 +/-5.68 vs. 15.77 +/- 5.97, p=0.01).

Conclusions: Cancer patients with hearing loss are very restricted in their

understanding of given information. As more hearing loss is seen as more

additional support is necessary to get a sucient information and consent.

at’s why, oncologists have to identify deaf and hard hearing patients and

should develop specic education tools for these groups.

Disclosure Statement: e authors declare no conict of interest.

720

Interprofessional counselling of cancer patients on

complementary and integrative health care (CIH):

Development and implementation of a training program

Birgit Kröger1; Lioba Lohmüller1; Ali Behzad2; Ursula Boltenhagen3;

JanGriewatz4; Stefanie Joos1; Anna Kaltenbach3; Nadja Klafke5;

Cornelia Mahler3; Barbara Stein6; Regina Stolz1; Jan Valentini1;

Markus Horneber7

11Institute of General Practice and Interprofessional Care, University Hospital

and Faculty of Medicine Tuebingen, Tübingen, Deutschland

2Department of Internal Medicine, Division of Pneumology, Paracelsus Medical

University, Klinikum Nürnberg, Nürnberg, Deutschland

3Department of Nursing Science, University Tübingen, Tuebingen, Deutschland

4Competence Centre for University Teaching in Medicine Baden-Wuerttemberg,

University of Tuebingen, Tübingen, Deutschland

5Institute of General Practice and Health Services Research, University Hospital

of Heidelberg, Heidelberg, Deutschland

6Department of Psychosomatic Medicine and Psychotherapy, Paracelsus

Medical University, Nuernberg, Nürnberg, Deutschland

7Department of Internal Medicine, Division of Pneumology, Paracelsus Medical

University, Nürnberg, Nürnberg, Deutschland

Background: Interprofessional collaboration among health care profes-

sionals is essential in oncology. CCC-Integrative is a study to investigate

the eects of interprofessional counselling on CIH in comprehensive can-

cer centers. Design and implementation of the training program for the

consulting nurses and physicians are reported.

Methods: e development of the program started with the analysis of

interprofessional models, current evidence on consultations on CIH,

situational demands and education standards. It incorporated outcomes

from a clinical trial (CONGO), a collaborative research project on CIH

(KOKON), elements of a training program for interprofessional team

building (TEAMc) and communication training (COMSKIL). e results

formed the didactical framework for the blended learning which con-

sisted of three main components: a web-based learning management sys-

tem (ILIAS) for content and learning materials, video-based face-to-face

expert led group and video-based sessions that facilitated and guided indi-

vidual and cooperative learning on case vignettes with dierent degrees of

complexity. Ongoing formative evaluation by questionnaires was used to

tailor the program to the needs of the participants. An interdisciplinary

task force coordinated all steps of the process.

Results: e 10-month training program consisted of 13 online sessions

with 3-6 hours duration and provided a web-based platform for concom-

itant learning. e training program contained lectures, case studies and

simulations of patient consultations. Eleven nurses and 11 physicians

completed the training.

Discussion: A novel training program for interprofessional counselling

on CIH was developed and successfully implemented. Further results and

implications will be presented and discussed.

Conclusion: e project could be used as a basis for a sustainable devel-

opment of interprofessional education on CIH for comprehensive cancer

centers.

Disclosure Statement: e authors declare no conict of interest.

725

Supporting patients during the trajectory of immunotherapy

– A qualitative study

Stefanie Mentrup1; Anne Letsch2; Anne Christin Rahn1

1University of Lübeck, Institute for Social Medicine and Epidemiology, Nursing

Research Unit, Lübeck, Deutschland

2University Hospital Schleswig-Holstein, Campus Kiel, Department of

Hematology and Oncology, Kiel, Deutschland

Background: Cancer patients undergoing immunotherapy need to be

accompanied and supported over the whole trajectory of the therapy.

Here, monitoring and identifying immune-related adverse events (irAE)

are important aspects to support the safety and management of cancer

patients. is qualitative study aims to explore how cancer patients under-

going immunotherapy are supported by healthcare professionals (HCPs)

and the challenges in clinical practice.

Methods: Semi-structured interviews were conducted with HCPs who

are in charge of patients treated with immunotherapy and with patient

representatives. Data collection and thematic analysis will be completed

by November 2021.

Result: Twelve interviews were already conducted with 6 nurses, 4 phy-

sicians and 2 patient representatives. Preliminary results indicate that

HCPs oen experience patients with planned immunotherapy adopting

a passive role in making decisions about the treatment. HCPs report to

provide information about immunotherapy and irAE stepwise to patients

and repeating them along the whole course of the treatment. e main

focus of the information about irAE aims to support patients’ self-man-

agement skills in monitoring symptoms. Side eects of the therapy are

regularly monitored in cancer patients. Some clinics have developed their

own checklists for this purpose. Most of the cancer patients seem to be

under pressure in continuing immunotherapy even if they experience

symptoms. erefore, one challenging situation in clinical practice is the

disruption or discontinuation of the therapy. HCPs try to give emotional

support in this situation although the daily throughput of patients in out-

patient clinics is high, and time is oen limited.

Discussion: e support of people undergoing immunotherapy is more

complex than the support in most standard care settings. HCPs must be

well trained and specialized on the specic needs of these patients.

Conclusion: More research is needed to design and evaluate a tailored

support program for patients with immunotherapy to provide holistic,

patient-centered care.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

727

The inuence of a combined vibration and sensomotoric

training on chemotherapy/ immunotherapy induced

polyneuropathy in the upper extremity – rst results

Stefanie Siebert; Jane Kersten; Sarina Kray1; Sarah Man;

Freerk T. Baumann

Uniklinik Köln - CIO, Med 1 - OTT, Köln, Deutschland

Background: Neurotoxic chemotherapy oen leads to peripheral poly-

neuropathies (PNP). Symptoms such as pain, tingling or numbness

restrict the patients’ quality of life. Previous studies show that sensorim-

otor and/or vibration training can have a positive eect on the symptoms

of the lower extremities. Whether preventive treatment with sensorimo-

tor and/or vibration training of patients receiving neurotoxic cytostatics

already inuences the PNP development of the upper extremities has not

yet been investigated.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts248

Method: During a 12-week training intervention, the subjects perform

two training sessions (T) of 60 minutes per week. At the beginning of

the intervention PNP symptoms must not have occurred. e subjects

are randomized into an intervention group and an active control group.

e IG conducts a sensorimotor and vibration training, while the CG

conducts a strength and endurance training. Before and aer the entire

intervention, ne motor skills are collected with the 20 cents test. EORTC-

QLQ-C30 (quality of life), Fact/GOG-Ntx (PNP symptoms) and VAS

(pain) are measured at T8 and T16 in addition to PRE and POST.

Results: e rst data collected do not yet show any trends. More precise

ndings can only be made aer the end of the survey period and the sta-

tistical evaluation.

Discussion: So far, positive changes to chemotherapy-induced PNP were

primarily shown in the lower extremities. erefore, positive tendencies

are expected in the upper extremities, too. To show the need and the fea-

sibility of reducing symptoms of PNP in the upper extremity the pilot

study is initiated. Vibration and sensorimotor training can be a suitable

treatment option. Aer evaluation of the results, a possible causality can

be determined.

Conclusion: e aim of this study is to demonstrate the preventive eects

of sensorimotor and vibration training on the symptoms of chemothera-

py-induced PNP of the upper extremities. Furthermore, the eects of the

intervention on quality of life, pain and functionality are explored.

Disclosure Statement: e authors declare no conict of interest.

735

Inuence of exercise behavior on fatigue syndrome (CRF)

and endurance capacity in cancer survivors – FatiGO-Study

Stefanie Siebert1; Jannike Salchow2; Melina Straub1; David Kroiher1;

Moritz Hahn1; Carrie-Ann Minto2; Marianne Sinn2; Anne Kollikowski3;

Claudia Loeer3; Freerk T. Baumann1

1CIO - Centrum für Integrierte Onkologie Uniklinik Köln, Med 1 - OTT, Köln,

Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Hubertus Wald Tumorzentum,

Universitäres Cancer Center Hamburg , Hamburg, Deutschland

3Universitätsklinikum Würzburg (UKW), Comprehensive Cancer Center (CCC)

Mainfranken, Würzburg, Deutschland

Background: e number of cancer survivors is steadily increasing.

Many still suer from side eects caused by the disease or the therapy.

Cancer- related Fatigue (CRF) is the most common side eect. Supervised

interventions seem to be the best way to ght CRF. Yet, cancer survivors

do not exercise enough and rarely meet general recommendations. ey

also show lower endurance capacity compared to healthy individuals. e

extent to which objectively measured physical activity behavior inuences

CRF and whether higher endurance capacity can improve the eects of

CRF are still largely unclear.

Methods: 15 cancer survivors with CRF who were at least 1 year up to 10

years post-therapy and had at least a fatigue score of ≥ 4 on the numerical

analog scale (NRS) participated in a 4-week multimodal exercise inter-

vention. Study participants were randomly assigned to 4 training groups

that included moderate- or high-intensity strength or endurance training,

and a control group. CRF was assessed pre (t0) and post (t1) interven-

tion using the EORTC QLQ- FA12 (FA12) questionnaire and was self-re-

ported by participants using NRS 3 times daily. Physical activity behavior

(MVPA) was assessed by accelerometer over 7 days during the interven-

tion and endurance capacity (VO2max) was assessed by spiroergometry

at t0 and t1.

Results: e FA12 showed signicant improvement for all subscales and

the Global Fatigue Score with p ≤ .5. e VO2max showed no signicant

improvement from t0 to t1. No correlations were found between FA12 and

VO2max, FA12 and MVPA, and MVPA and NRS. In contrast, a highly

signicant correlation was found for VO2max t0, t1 and MVPA with

p< .001.

Conclusion: Exercise intervention was safe to perform for patients aer

completing cancer treatment with CRF (NRS ≥ 4). Both aerobic and resis-

tance exercise at high and moderate intensity were eective to improve

CRF and great exercise behavior has benecial eects on endurance

performance. Going further, there is evidence that increased endurance

capacity positively aects CRF.

Disclosure Statement: e authors declare no conict of interest.

741

Module preferences and compliance in dierent exercise

modules for young adults with cancer – YOUEX study

Annelie Voland1,2; Timo Niels3; Inaam El-Rajab1,2; Verena Krell4;

Miriam Götte5; Maximilian Köppel1,2; Joachim Wiskemann1,2

1Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

2Universitätsklinikum Heidelberg, Heidelberg, Deutschland

3Uniklinik Köln, Centrum für Integrierte Onkologie (CIO) Köln, Köln, Deutschland

4Charité - Universitätsmedizin Berlin, Abteilung Sportmedizin, Berlin,

Deutschland

5Universitätsmedizin Essen, Zentrum für Kinder- und Jugendmedizin, Essen,

Deutschland

Background: To date, strong evidence supports the persuasive positive

eects of exercise on cancer treatment-related side eects. Dierent

approaches of oncological exercise programs have been established,

however, the special interests of younger adults with cancer, including

the integration of online-tools, have rarely been considered in exercise

interventions.

Objective: e aim of this study is to analyze three dierent exercise mod-

ules on module preferences and compliance data.

Methods: is 12-week (w) exercise intervention included young adults

with cancer aged 18–39 years who currently have or had a cancer diagno-

sis within the past 5 years. Participants may choose between three exercise

modules (M1: group-based, social media exercise program once a week,

M2: individual home-based training with an online- training app at least

once per week, M3: participation in an in-person exercise program close

to place of residence). e selected module could be replaced or amended

by another module aer 6w (T1).

Results: From n=92 participants who started at T0, 37.0% patients chose

M1, 54.3% M2 and 8.7% M3. 87% (n=80) of patients could be analyzed

at the T1 timepoint (6w) and 80.4% (n=74) at the T2 timepoint (12w).

Dropout rate from T0-T2 was 19.6% (n=18). Patients who only partici-

pated in M1 the whole 12w duration had an overall exercise compliance

of 47,1%. Further, 77,1% of participants who only participated in M2 for

12w, made usage of our training app on average 1x/w. ere are no adher-

ence results for M3. At T1 42.5% (n=34) of patients switched (n=23) or

amended (n=11) their initial module with another aer 6w.

Discussion: Regarding the initial module choice, patients preferred indi-

vidual app-based exercise programs compared to xed group-based exer-

cise sessions. 12w compliance-rate was higher in M2 compared to M1.

Less than half of the participants changed their module aer 6w.

Conclusion: Individual home-based exercise programs seem to be more

attractive and suitable to the special needs of young adults with cancer

than timed once per week online-exercise sessions.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 249

753

Treatment-related side eects, perceived barriers and

knowledge regarding exercise in patients receiving

immunotherapy: A cross-sectional online survey

Nils Scharath1; Philipp Zimmer2; Elke Jäger3; Katharina Graf1

1Institut für onkologische Sport- und Bewegungstherapie, UCT Frankfurt,

Krankenhaus Nordwest, Frankfurt, Deutschland

2Institut für Sport und Sportwissenschaft, TU Dortmund, Dortmund,

Deutschland

3Klinik für Onkologie und Hämatologie, Krankenhaus Nordwest, Frankfurt,

Deutschland

Background: Although extensive evidence underlines the potential of

exercise as a supportive strategy in oncology, the availability of specic

counselling and exercise programs varies considerably between treatment

regimens and phases. Especially for patients with novel anticancer thera-

pies, information about exercise-related aspects such as exercise knowl-

edge, program availability and barriers are missing. us, this survey

examines treatment-related side eects as well as the knowledge and bar-

riers regarding exercise in patients with immunotherapeutic anticancer

treatment.

Methods: An online cross-sectional survey, partly consisting of standard-

ized and validated questionnaires, was conducted via the distribution of

social media (cancer survivor groups) over the timescale of three months.

Results: Up to date 55 participants (m=14, f=41; (51±12,8y) with ongoing

(n=39) or nished (n=16) immunotherapy completed the survey. More

than 60% of the participants experienced cancer-/therapy-related side

eects such as pain (63%), dermatological problems (65%), fatigue (61%),

polyneuropathy (73%), and cognitive impairments (62%) for at least 3x/

week. Perceived barriers to exercise were mainly fatigue (49%), that exer-

cise is not a routine (40%), no tting exercise program (30%), and reduced

physical function (35%). 84% of the patients with ongoing immunother-

apy stated that they were not or poorly informed about exercise as a sup-

portive strategy.

Discussion: e results indicate that patients undergoing immunother-

apy encounter various side eects, that might be mitigated via individually

tailored exercise. Simultaneously, the patients perceive dierent barriers

to exercise and are insuciently informed regarding exercise benets

during their oncological care.

Conclusion: Information and advising strategies targeted to the needs of

patients undergoing immunotherapy seem to be necessary to improve the

knowledge about exercise, to reduce barriers and thus to promote physical

activity and participation in regular exercise routines.

Disclosure Statement: e authors declare no conict of interest.

772

Exercise therapy with multiple myeloma patients: Evaluation

of an oncologic care structure on feasibility, adherence, and

ecacy

Freerk T. Baumann; Michael Mendes Wefelnberg

Universitätsklinikum Köln, Klinik 1 für Innere Medizin, Centrum für Integrierte

Onkologie (CIO) Köln Bonn, Köln, Deutschland

Background: Multiple myeloma (MM) is a severe haemato-oncological

disease with high mortality and increasing incidence rate. Since evidence

on exercise therapy with MM patients remains quite limited, this study

examines real-life data of an oncologic care structure regarding feasibility,

adherence, and ecacy.

Methods: A prospective data evaluation of MM patients who participated

in the oncologic training and exercise therapy (OTT) at the Cologne

University Hospital between 2012 and 2019 was conducted. e data was

successively reduced to four cohorts, intention-to-treat (ITTC), safety

(SC), adherence (AC) and ecacy (EC) and then, evaluated descriptively,

by means of correlation analysis as well as group and time comparisons.

Result: e SC (N = 26) attended exercise therapy on average about one

session per week over a period of eight month. Roughly one third dropped-

out within three months. In the AC (N = 15) BMI at baseline exhibited a

strong and very signicant negative correlation with exercise adherence.

In the EC (N = 8) a signicant improvement in physical functioning and a

tendency towards signicance in fatigue reduction between two MPs at a

median distance of 20 sessions (range: 16 -30) were observed. No adverse

events were documented.

Discussion: Attending MM patients demonstrated feasibility of exercise

therapy. Yet, due to data insuciencies, impact of severe symptoms (e.g.,

bone lesions) as well as mortality on drop-out rates and relatively low

exercise frequency remains speculative. e ndings are generally limited

by the applied reduction process, the post hoc specication of evaluation

methods and unknown circumstances of patients’ admission to OTT.

Conclusion: Exercise interventions for MM patients at the OTT are safe

and feasible. Associations between BMI and exercise adherence as well

improvements in physical functioning and fatigue provide indications for

future conrmatory study designs.

Disclosure Statement: e authors declare no conict of interest.

778

Hygienic concept for oncology exercise therapy treatment

(OTT) with cancer patients during COVID-19 pandemic at the

University Hospital Cologne

Constanze Handmann; Freerk Baumann

Uniklinik Köln, Köln, Deutschland

Background: During the pandemic of COVID-19 most hospitals sig-

nicantly reduced non-emergency admissions and services due to the

increased risk of viral infection. As a result, the recommended self-iso-

lation for cancer patients during pandemic may lead to physical inactiv-

ity and prolonged sitting time. In addition to the negative side eects of

treatment, this lack of physical activity and exertion has further negative

implications for their health, such as decrease in physical performance

and health related quality of life.

Methods: To address this problem the OTT (Onkologische Trainings-und

Bewegungstherapie) of the University Hospital Cologne located in the

Center for Integrated Oncology (CIO) implemented a Hygienic Concept

to ensure safe training session with the physical therapists during COVID

-19 pandemic situation

Result: e need of physical exercise for cancer patients on the one hand,

and protection against the spread of coronavirus on the other hand, infec-

tion control had to be given priority. Although the hygienic concept was

used in the time between September 2020 till August 2021, also during

lock down situation in Cologne. 260 oncologic patients have taken part

in the oncologic exercise therapy. None of the training patients infected

himself with coronavirus during that time period.

Discussion: e hygienic concept was proven safe. Taking into account

the current infection situation and the above-mentioned objectives, the

resumption of regular exercise therapy for cancer patients is necessary but

must take place in another Hygienic Concept compared to non-pandemic

situations.

Conclusion: It should be noted that essential hygiene and infection pro-

tection measures must continue to be observed by all persons involved

in the clinical setting. In addition, it is important to recognize emerging

chains of infection at an early stage and to prevent their spread. It is safe

for cancer patients to use exercise therapy during pandemic situations

when used adapted hygienic concepts.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts250

826

Comparative evaluation of subjectively reported and

objectively measured physical activity in young adults after

childhood, adolescent or young adult cancer within the CARE

for CAYA study

Simon Elmers1; Stanislaus Gröhnke1; Carrie-Ann Minto1; Alexander Stein1;

Jannike Salchow1

1Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center

Hamburg (UCCH), Hamburg, Deutschland

Background: Due to multimodal therapy, the survival rate for cancer in

children, adolescents and young adults (CAYA) has increased. e higher

number of survivors leads to a higher number of late and long-term eects.

Aproximatelly two-thirds of AYAs report therapy-related long-term side

eects. Physical activity (PA) is a well-established method to reduce these

side eects. erefore, it is important to know about the PA behaviour of

cancer survivors. In order to provide insight, various objective and sub-

jective methods of recording PA within the CARE for CAYA study were

compared, with the goal of determining which was the most valid.

Methods: Subjectively reported moderate-to-vigorous PA (MVPA) was

recorded by a physical activity diary (BWT), the CARE for CAYA screening

questionnaire (SF-CfC), and physical activity questionnaire (BSA). Data

was compared with objective measures (MVPA-time, steps), as collected

by the ActiGraph wGT3x-BT. Participants were divided into a suciently

active (≥12,500 steps/day) or insuciently active (<12,500 steps/day)

group. To detect a lack of PA, subjective methods were compared (i.e.

statistically signicant dierences between groups). Receiver Operating

Characteristic (ROC) analysis were used to determine model quality. For

objective measures, motivational and weekend-eects were tested.

Result: 165 CAYAs (mean age 26.5 years, 71.5% female) were included.

SF-CfC (p = 0.489, area-under-the curve (AUC) for ROC analysis: 0.511)

and BSA (p = 0.137, AUC = 0.576) failed to show evidence of signicant

dierences compared to objective measures. BWT (p = 0.001, AUC =

0.682) achieved statistical signicance.

Discussion: Of the compared subjective methods, BWT is the most eec-

tive at identifying a lack of PA. However, it showed weaknesses in deter-

mining PA levels.

Conclusion: With these ndings, it is recommended to continue the use

of both subjective- and objective-measures of PA. Further research should

investigate if there is a motivational eect by wear-ing the ActiGraph and

if there is a dierence in PA levels on weekends.

Disclosure Statement: e authors declare no conict of interest.

874

Feasibility of a Fascia-training in Patients Undergoing

Allogeneic Hematopoietic Cell Transplantation

Sandra Weigmann-Faßbender1,2,3; Hanna Ulbricht1,2,3;

Marianne de Schultz2; Christine Pawandenat1; Desiree Kunadt1,2,3;

Michaela Wol4; Nadine Giesemann2,3,4; Katja Prate1; Johannes

Schetelig1,2,3; Martin Bornhäuser1,2,3; Friedrich Stölzel1,2,3; Nadja Seidel1,2,3;

Friederike Stölzel1,2,3

1University Hospital Carl Gustav Carus Dresden, Dresden, Deutschland

2Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden,

Deutschland

3National Center for Tumor Diseases Dresden (NCT/UCC), Dresden, Deutschland

4Technical University Dresden, Dresden, Deutschland

Background: Regular Physical Activity (PA) is associated with various

benets for cancer patients. Patients that undergo allogeneic hematopoi-

etic cell transplantation (alloHCT) spend many weeks of treatment in an

isolated environment, oen with little room for exercise. is pilot study

investigated feasibility of a daily performed, unassisted fascia-training and

its eects on back and foot pain, back exibility and quality of life.

Methods: Eighteen alloHCT-patients were randomized to an intervention

(IG: n=9; 60.7± 9.2 years) or control group (CG: n=9; 54.0± 15.5 years)

and assessed from one week before to three weeks aer transplantation

(t0 – t3). CG received standard care physical therapy and IG performed

additionally fascia-training for back and feet twice daily. For both IG and

CG at baseline and three time points aer alloHCT back and foot pain,

back exibility, muscle tone and quality of life were assessed.

Result: Overall, fascia-training was well accepted. No increase in hema-

toma formation was observed. IG reported a trend towards reduction in

back pain from pre- to post-intervention (p = .074), whereas CG showed

a slight increase in back pain at t3 (p = .257). IG also improved back ex-

ibility (-1.79 ± 5.5 cm; p = .397) whereas a decline of back exibility was

observed in CG (+2.71 ± 5.6 cm; p = .167). No dierences between groups

were found for muscle tone. No signicant improvements in quality of life

were reported at t3.

Discussion: is is the rst study investigating feasibility and potential

eects of a special fascia-training in alloHCT-patients. e sample was

small and heterogeneous concerning age, gender and underlying diseases,

but fascia-training was feasible, safe and benecial.

Conclusion: Results of this pilot study suggest that fascia-training has

the potential to improve back exibility, reduce back pain and might be

a valuable component for physical therapy in alloHCT-patients. Further

investigations are necessary to conrm initial ndings of this pilot study.

Disclosure Statement: e authors declare no conict of interest.

951

Interprofessional Communication about Complementary and

Integrative Health (CIH): Development and Implementation of

a Training Program

Ali Behzad1,2; Barbara Stein3; Anna Kaltenbach4; Lioba Lohmüller5;

Birgit Kröger5; Ursula Boltenhagen4; Stefanie Joos5; Nadja Klafke6;

Cornelia Mahler4; Regina Stolz5; Jan Valentini5; Markus Horneber2

1Department of Internal Medicine, University Hospital of Erlangen, Division of

Hematology and Oncology, Erlangen, Deutschland

2Department of Internal Medicine, Paracelsus Medical University, Division of

Pneumology, Nürnberg, Deutschland

3Department of Psychosomatic Medicine, Paracelsus Medical University,

Nürnberg, Deutschland

4Department of Nursing Science, University Tuebingen, Tuebingen,

Deutschland

5Institute of General Practice and Interprofessional Care, University Hospital and

Faculty of Medicine Tuebingen, Tuebingen, Deutschland

6Institute of General Practice and Health Services Research, University Hospital

of Heidelberg, Heidelberg, Deutschland

Background: In the controlled study `CCC-Integrativ´, interprofessional

teams consisting of nurse practitioners and physicians counsel cancer

patients on CIH. e counselling aims to foster patients’ informed deci-

sion making and strengthen self-ecacy. During the study start-up phase,

teams underwent a specialist training on CIH. Here, we report on the

embedded communication skills training (CST).

Methods: Experts in health care communication designed and led

the CST. Design included the following steps: Analysis of challenges

of interprofessional counselling on CIH, adaptation of an existing CST

for medical advice about CIH (COMSKIL-approach developed in the

KOKON-project), its integration into the specialist training on CIH and

adjustment for online training due to the pandemic. Formative evaluation

was used to adapt the training to the participants’ needs.

Results: Based on the theory-founded concept of the COMSKIL pro-

gram, the CST taught core elements of medical communication, specic

elements of interprofessional counselling and motivational interviewing.

It addressed typical situations using case analyses, patient vignettes, role

plays and simulated patients with gradual increase in complexity. e CST

was manualized and 11 nurses and 11 physicians underwent the training.

Discussion: We developed an innovative online CST for nurse practi-

tioners and physicians to foster patient-oriented and motivating counsel-

ling of cancer patients on CIH. e CST was embedded in a specialist

training on CIH, oering the unique opportunity to combine knowledge

transfer and practice of communication skills. It can be used online and

in presence both as a CST in oncology and as an element of an advanced

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 251

training course on CIH. Course, content and evaluation of the CST will

be presented.

Conclusion: Interprofessional counseling on CIH can eectively be

taught online and implemented in advanced training courses.

Disclosure Statement: e authors declare no conict of interest.

974

Feasibility and adherence of a playful sensorimotor training

for children and adolescents during acute cancer therapy

Theresa Kömpel1; Sarah Otten2; Meinolf Siepermann3;

Clémentine Bischo4; Melanie Reitz2; Fiona Streckmann5;

Julia Däggelmann2; Wilhelm Bloch2; Vanessa Oschwald2

1Institut für Kreislauorschung und Sportmedizin, Abteilung Molekulare und

zelluläre Sportmedizin, Köln, Deutschland

2Institut für Kreislauorschung und Sportmedizin, Abteilung Molekulare und

zelluläre Sportmedizin, Am Sportpark Mpngersdorf 6, Köln, Deutschland

3Kliniken der Stadt Köln gGmbH , Kinderkrankenhaus Amsterdamer Straße,

Abteilung für Kinderonkologie und Kinderhämatologie, Köln, Deutschland

4Universität Basel, Deparment für Sport, Bewegung und Gesundheit, Abteilung

Bewegungs- und Trainingswissenschaften, Basel, Schweiz

5Universität Basel, Deparment für Sport, Bewegung und Gesundheit, Abteilung

Bewegungs- und Trainingswissenschaften, Basel, Schweiz

Purpose To determine the feasibility and satisfaction of sensorimotor

training (SMT) which is applied using an age-specic card game during

acute cancer therapy.

Methods A four-week SMT intervention is conducted in pediatric cancer

patients (age 6-21). Training is performed 3x/week (every 2nd supervised)

and consists of 3-6 sensorimotor exercises (5 reps à 20s with 20s rest, 1min

rest between exercises). To respect self-determination during therapy,

patients can individually choose severity level using a specic card game,

which allows them to combine various positions, surfaces and dual tasks.

Feasibility and training satisfaction are assessed using a self-developed

questionnaire aer the intervention.

Results Study recruitment started in March 2022. Preliminary results will

be available and presented at the congress. Positive outcomes are expected

regarding training feasibility and training satisfaction.

Discussion SMT can induce neural adaptations. In pediatric oncology,

SMT is therefore applied to improve sensory and motor dysfunctions that

impact developmental milestones. Initial eects could already be demon-

strated in pediatric cancer survivors. Studies in adults have shown that

SMT is a promising training method1. For children and adolescents during

acute cancer therapy, SMT therefore seems to be a promising training

method, as well. By using a specic card game to set severity level, indi-

vidual adaptations to the patients’ health status and promotion of self-de-

termination are possible. Also, training motivation can be augmented.

Conclusions For children and adolescents during acute cancer therapy,

SMT can be a promising method to maintain or restore crucial bal-

ance skills. In this context, a playful implementation with a card game,

adapted to individual abilities, can promote satisfaction, fun and training

motivation.

References

1 Streckmann F, Balke M, Cavaletti G, Toscanelli A, Bloch W, Décard BF, Leh-

mann HC, Faude O (2021) Exercise and Neuropathy: Systematic Review with

Meta-Analysis. Sports Medicine 52(5): 1043-1065

Disclosure Statement: e authors declare no conict of interest.

987

Perceived eects of a 4-Week-Sensorimotor Training-

Intervention in childhood cancer patients on selected physical

abilities

Melanie Reitz1; Sarah Otten1; Stefan Balzer2; Vivien Lösse2;

Theresa Kömpel1; Julia Däggelmann1; Wilhelm Bloch1; Vanessa Oschwald1

1Deutsche Sporthochschule Köln, Institut für Kreislauorschung und

Sportmedizin, Molekulare und zelluläre Sportmedizin, Köln, Deutschland

2Kinderkrankenhaus Amsterdamer Straße, Köln, Deutschland

Background: To determine the perceived eects of a sensorimotor train-

ing (SMT) on selected physical abilities in childhood cancer patients

receiving acute medical treatment.

Methods: A 4-week SMT-Intervention in childhood cancer patients

receiving acute medical treatment (mixed diagnoses, 5-21 years) is con-

ducted. SMT training is performed 3x/week (each 2nd session is super-

vised). 3-5 exercises/session are performed (5 reps à 20s followed by 20s

rest, 1 min rest between exercises). Participants select the exercise intensity

by combining dierent exercise positions, surfaces and dual tasks using a

specic card-game. Perceived eects are assessed using a self-developed

questionnaire (5-point-likert scale) following the 4-week intervention.

Result: Study recruitment started in March 2022. Preliminary results will

be available and presented at the congress. We expect improvements in

perceived physical abilities.

Discussion: Children with cancer oen suer from physical perfor-

mance limitations, which may impact their mobility and physical activity.

Further, SMT is a form of neuromuscular training to promote balance and

functional performance1. us, it may be a benecial exercise strategy in

pediatric oncology. Perceived and objective eects should be investigated.

Conclusion: SMT may be eective to promote balance and related phys-

ical abilities in children with cancer. SMT may be considered as an addi-

tional exercise therapy strategy.

Indication of source:

1 Streckmann, F., Rittweger, J., Bloch, W., Baumann, F.T. (2014). Bewegungs-

empfehlungen bei Chemotherapie-induzierter peripherer Polyneuropathie.

Bewegungstherapie und Gesundheitssport, 30, 179-182.

Disclosure Statement: e authors declare no conict of interest.

1040

Eects of exercise on chemotherapy-induced peripheral

neuropathy, cancer-related fatigue and sleep quality during

neurotoxic chemotherapy

Jana Müller1; Charlotte Kreutz2; Andreas Schneeweiss3;

Georg Martin Haag4; Karen Steindorf2; Markus Weiler5;

Joachim Wiskemann1

1Heidelberg University Hospital, National Center for Tumor Diseases (NCT)

Heidelberg, Division of Medical Oncology, Working Group Exercise Oncology,

Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Division of Physical Activity,

Prevention and Cancer, Heidelberg, Deutschland

3Heidelberg University Hospital, National Center for Tumor Diseases (NCT)

Heidelberg, Division of Gynecological Oncology, Heidelberg, Deutschland

4Heidelberg University Hospital, National Center for Tumor Diseases (NCT)

Heidelberg, Division of Medical Oncology, Heidelberg, Deutschland

5Heidelberg University Hospital, Department of Neurology, Heidelberg,

Deutschland

Background: (Neurotoxic) Chemotherapy can have profound negative

eects at the biopsychosocial level. is secondary analysis extends pre-

vious analyses with the aim of comprehensively investigating whether

a sensorimotor- (SMT) and resistance training (RT) may aect subjec-

tively perceived chemotherapy-induced peripheral neuropathy (CIPN)

symptoms [1] as well as fatigue and sleep quality during neurotoxic

chemotherapy.

Methods: 170 patients were randomized to SMT, RT or usual care (UC).

Patients exercised 3×/week (105 min/week) during neurotoxic chemother-

apy (mean length: 20 weeks). CIPN symptoms (EORTC CIPN20), fatigue

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts252

(MFI), and sleep quality (PSQI), were assessed before and 3 weeks aer

neurotoxic chemotherapy. Analysis-of-covariance models were applied

(covariates: age, gender, neurotoxic chemotherapy class, baseline value of

the respective dependent variable, and optional CIPN symptoms).

Result: CIPN symptoms, general, physical, and mental fatigue increased

in all groups (p<.05), while sleep quality remained unchanged. Intention-

to-treat analyses (N=159) revealed no dierences. Exploratory per-pro-

tocol analyses (training attendance rate ≥ 67%; N=89) indicated that

sensory symptoms in the feet, general and physical fatigue and reduced

activity increased less during chemotherapy in the adherent exercisers

(pooled group: SMT+RT) compared to UC (p<.04). Inclusion of CIPN

symptoms as a covariate resulted in non-signicant eects for all fatigue

dimensions except general fatigue.

Discussion: In contrast to other research, sleep quality was not aected

by exercise, probably due to a ceiling eect. Of note, the eects on fatigue

were inuenced by CIPN symptoms, raising the question if the MFI is a

valid questionnaire for detecting fatigue in CIPN patients.

Conclusion: SMT and/or RT may alleviate CIPN symptoms [1]

and probably fatigue in patients undergoing neurotoxic chemotherapy, if

an appropriate training stimulus is achieved.

e authors declare no conict of interest.

Reference:

[1] Müller 2021 BJC https://doi.org/10.1038/s41416-021-01471-1

Disclosure Statement: e authors declare no conict of interest.

Surgical Oncology

Best-of-Abstract-Vortrag

396

Mortality and complication management after surgery for

Esophageal, Gastric, Pancreatic and Liver cancer patients

based on the DKG minimum caseloads

Konstantin Uttinger1; Johannes Diers2; Christoph-Thomas Germer3;

Armin Wiegering3

1Uniklinikum Leipzig, Viszeralchirurgie, Leipzig, Deutschland

2Krankenhaus Havelhöhe Berlin, Innere Medizin, Berlin, Deutschland

3Uniklinikum Würzburg, Chirurgie I, Berlin, Deutschland

Background: e German Cancer Society (DKG) board certies cancer

centers in treating esophageal, gastric, liver and pancreatic cancer among

others. One major criterion used is annual surgical caseload. To this date,

there has been no systematic verication of the number of yearly surgical

resections set by DKG with regards to in-house mortality and failure to

rescue (FtR).

Methods: is is a retrospective analysis of anonymized nationwide hos-

pital billing data (DRG data, 2009-2017). In correspondance with the

Ocial Oce of Statistics in Germany and their data protection guide-

lines, patients were identied using ICD and/or OPS codes as certied

by the DKG.

Results: 171,099 patients were identied based on DKG certication,

including 30,810 Esophageal, 54,155 Gastric, 57,343 Pancreatic and

28,791 Liver resections. Overall in-house mortality ranged between 6.2%

(Gastric resections) and 8.1% (Pancreatic resections). Dierences in

in-house mortality between hospitals which fullled the surgical (annual)

minimum caseload (SMC) and those which did not fulll SMC on average

was 2.9% (5.3% vs 8.2%) in Esophageal, 2.0% (4.8% vs 6.8%) in Gastric

and 3.7% (6.1% vs 9.8%) in Pancreatic cancer patients, while it was -0.6%

(7.6% vs 7.0%) in Liver cancer patients. Complication occurrence rates

for Esophageal, Gastric and Pancreatic resections were similar in hospitals

which did or did not fulll SMC while FtR in hospitals fullling SMC was

signicantly lower in case of occurrence of any complication. In addition,

a statistical model demonstrated that SMC should be risen in esophageal,

gastric and pancreatic resections.

Discussion: In Liver cancer patients, outcome has no clear correlation

with annual surgical volume suggesting that dierent quality indicators

may be of signicance in this patient group.

Conclusion: is study demonstrates an association between fulllment

of SMC set by DKG and lower FtR in Esophageal, Gastric and Pancreatic

cancer patients and improved in-house mortality rate.

Disclosure Statement: e authors declare no conict of interest.

Poster

601

SOCIUS Mentoring - A novel approach to motivate and

prepare students for a career in surgical oncology

Rüdiger Klapdor1; Peter Hillemanns1; Hermann Hertel1; Kai Timrott2;

Florian Imkamp3,4

1Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule

Hannover, Hannover, Deutschland

2Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische

Hochschule Hannover, Hannover, Deutschland

3Klinik für Urologie, Vinzenzkrankenhaus Hannover, Hannover, Deutschland

4Klinik für Urologie und urologische Onkologie, Medizinische Hochschule

Hannover, Hannover, Deutschland

Background: e shortage of physicians poses increasing challenges

to surgical disciplines, especially in university medicine. Students lose

interest in surgery during their studies or during their practical year.

To counteract this development, students need to be more strongly and

sustainably inspired. e Surgical Oncology Curriculum for individual

support of ambitious students (SOCIUS) is intended to optimally prepare

students for a career in university surgical oncology.

Methods: As a cooperation between Gynecology, Visceral Surgery and

Urology, a one-year mentoring program for outstanding students was

planned, consisting of six modules and 80 teaching units. Core elements

of the program, in addition to mentoring by clinically and scientically

successful physicians, are the training of operative skills on state-of-the-

art simulators and, in particular, specic so skills that are necessary for

a successful career. Visitations in the participating clinics and congress

participations round o the program. e impact of the program is eval-

uated through the change in participants’ condence and surgical skills

using standardized tests.

Result: In two years, 20 students were selected from 100 excellent appli-

cations. e students signicantly improved their surgical skills and so

skills. is was documented by increased condence scores. In addition,

the students stated that they had specied their career goals and gained

more self-condence in surgery, as well as seeing more potential in a sur-

gical career. Satisfaction with the program is also reected in the absolute

recommendation rate of the course to friends (MW 5.0, scale 1-5).

Conclusion: Individual support of students through a combination of

mentoring and skills training is a promising way to prepare and motivate

students for their residency in surgical disciplines and thus to counteract

the shortage of young talent in surgical disciplines.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 253

604

Peritoneal tumor lesions (PTLs) - spectrum of diagnoses,

surgical interventions and outcome in a representative case

series at a tertiary center

Frederike Weber1; Tatiana Oksentyuk Polyakova1; Christine March2; Kai

Weger3; Roland S. Croner1; Frank Meyer1

1Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie,

Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland

2Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg

A.ö.R., Magdeburg, Deutschland

3Institut für Pathologie, Universitätsklinikum Magdeburg A.ö.R., Magdeburg,

Deutschland

Aim: Exemplary demonstration of 7 cases with rare PTLs and their

histopathological results in abdominal surgery emphasizing biological

diversity.

Method: Representative selection of scientic case reports

Results:

1) Diverticulum of the jejunum with pancreatic metaplasia: Intraoperative

incidental nding of a jejunal PTL during gynecological surgery of

endometrium carcinoma lead to segmental resection and reconstruc-

tion with side-to-side jejunojejunostomy.

2) Twisted “appendix epiploicae” (with lipobrosis and necrosis of the

appendix): Patient with progressive abdominal pain in the right lower

abdomen was diagnosed with acute appendicitis followed by laparo-

scopic appendectomy with partial resection of the greater omentum.

3) Acute epiploic appendagitis: In laparoscopic hernioplasty of incarcer-

ated trocar hernia, a suspicious inamed fatty tumor-like tissue was

resected from the descending colon.

4) Primary peritoneal cancer: During explorative laparotomy for ovar-

ian tumor, multiple 8- to 15-mm PTLs were found and subsequently

resected along with radical hysterectomy resulting in R0 resection sta-

tus (5 years ago, mastectomy for breast cancer).

5) Primary serous papillary adenocarcinoma of the peritoneum (his-

tological nding): Patient underwent subtotal peritonectomy, right

hemicolectomy, partial resection of the urinary bladder and HIPEC.

6) Pseudomyxoma peritonei: Patient with PTL (PCI: 32) of unknown

origin underwent palliative ileocoecal resection including 4 PTLs of

mucinous adenocarcinoma.

7) Plant food ingredients (plus older fat necrosis mimicking PTL): In a

patient with chronic subileus, small PTLs were found causing scar-

ring adhesion of the jejunum aer previous appendectomy and ileum

resection.

Conclusion: PTL can comprise diverse origins and entities.

Histopathological investigation and close cooperation of the pathologist

and surgeon can be considered a substantial prerequisite (necessary due to

their rareness) for denite diagnosis-nding, following decision-making

and further therapeutic steps using various modi.

Disclosure Statement: e authors declare no conict of interest.

767

Does VO2-peak provide a prognostic value in esophagectomy

and gastrectomy for post-operative outcomes?

Timo Niels1; Christoph Tobias Heinrich Baltin2; Guido Kosanke3; Ulrich

Klaus Fetzner4; Arnulf H Hoelscher5; Elfriede Bollschweiler3; Jan-Hendrik

Naendrup1; Freerk T. Baumann1

1Department I of Internal Medicine, University, Hospital of Cologne,

Deutschland, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf,

Deutschland

2Department of Orthopaedics and Trauma Surgery, , University Hospital of

Cologne, Cologne, Deutschland

3Medical Faculty University of Cologne, Deutschland

4Department of General Surgery, Visceral-, Pediatric-, Thoracic- & Endocrine

Surgery, Johannes Wesling, University Hospital of Minden, Deutschland

5Contilia Centre for Esophageal Diseases, Elisabeth Hospital Essen, Essen,

Deutschland

Background: Esophagectomy and gastrectomy are procedures with con-

siderable physical burden and intense post-operative care for the patient.

e physical condition seems to be relevant in prediction of the post-op-

erative care. e VO2-peak value provides the gold standard for the

assessment of the physical performance. erefore, this pilot-study exam-

ined the prognostic value of the VO2-peak on post-surgery outcomes in

esophageal and gastric cancer patients.

Methods: In this prospective cross-sectional study, patients scheduled for

esophagectomy or gastrectomy were examined 24h-prior surgery regard-

ing their functional VO2-capacity (VO2-peak). e post-operative com-

plications according to Clavien-Dindo (CD) grade 3b or above, Intensive

Care Unit (ICU-) days and length of hospital stay were documented fol-

lowing surgery.

Result: e functional capacity was signicantly reduced in 34/35

included patients compared to gender-, age and body weight-matched

norm-values. Following surgery, the average hospital stay was 19,6 days,

the mean ICU-stay 5,8 days and patients experienced a mean of 0,46 com-

plications of CD grade 3b/above. No signicant correlations were found

between VO2-peak values and post-operative outcomes. No predictor

power of VO2-peak was observed. A subgroup comparison of patients

with a VO2-peak <17ml/min/kg and =/>17ml/min/kg suggested descrip-

tive dierences in post-surgery outcomes favouring the tter subgroup,

but non-signicantly.

Discussion: We observed heavily reduced physical perfomance capacity

pre-surgery, possibly caused by previous neoadjuvant treatment proce-

dures. e prognostic-value of VO2-peak remains uncertain within this

pilot-study due to noticeable descriptive dierences but no signicant

correlations or predictor power, potentially limited by the small-sized

population.

Conclusion: e impaired functional capacity shown in this pilot-study

may strengthen the rational for exercise programs during neoadjuvant

and pre-surgery phase.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts254

895

Shortening time to diagnosis in malignant spinal lesions using

a novel diagnostic fast track- a multidisciplinary approach

Annika Heuer1,2; Leon-Gordian Koepke2; Martin Stangenberg2;

André Strahl3; Marc Dreimann2; Lutz Welker4; Carsten Bokemeyer5;

Lennart Viezens2; Anne Marie Asemissen5

1Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center

Hamburg-Eppendorf, Hamburg, Deutschland

2Department of Trauma and Orthopedic Surgery, University Medical Center

Hamburg-Eppendorf (UKE), Division of Spine Surgery, Hamburg, Deutschland

3Department of Trauma and Orthopedic Surgery, University Medical Center

Hamburg-Eppendorf (UKE), Division of Orthopedics, Hamburg, Deutschland

4Institute of Pathology with the Sections Molecular Pathology and

Cytopathology, University Medical Center Hamburg-Eppendorf (UKE),

Hamburg, Deutschland

5Hubertus Wald University Cancer Center, University Medical Center Hamburg-

Eppendorf (UKE), Department of Oncology, Hematology and Bone Marrow

Transplantation with Section Pneumology, Hamburg, Deutschland

Background: Up to 20% of patients (pt) with prior unknown malignancy

present initially due to spinal lesions. Histopathological (HP) examination

represents the diagnostic gold standard. However, decalcication of bone

samples takes up to 14 days. Despite its potential for quicker diagnostic

information, intralesional aspiration cytology (IAC) has not been rou-

tinely performed during spine surgery. We introduced supplementary IAC

in 2020 as part of a multidisciplinary approach aiming to shorten time to

diagnosis (TTD). Methods: Pt requiring spine surgical intervention due to

spinal lesions of unknown origin received intraoperative IAC via transpe-

dicular biopsy of the vertebral body. Cytologic specimens were evaluated

using May-Gruenwald-Giemsa stain by a board-certied hemato-oncolo-

gist. HP specimen analyses were performed standardized. Retrospectively

statistical analysis was performed using the student’s t-test and Cohen’s

kappa.

Result: To date, 50 pt (38% female) with a median age of 48.9 ± 30.1 years

were included. 5 pt showed no evidence of malignancy. Multiple myeloma

and solid neoplasia were diagnosed in 22 and 66 % respectively by HP.

Compared to HP, IAC detected malignant lesions with a sensitivity of

0.97, specicity of 0.80, and diagnostic certainty of 0.9. With respect to

detection of malignant cells and dierentiation between hematologic or

solid neoplasia, concordance between HP and IAC was 0.922 (kappa).

Mean TTD using IAC was 1.8 ± 1.8 d, whereas HP results were received

aer 8.8 ± 3.5 d (p < 0.001). In 13 pts (26%) specic oncologic therapy

was initiated before the nal HP report was available, based on clinical

variables, staging, and IAC.

Discussion: IAC shows high sensitivity, specicity as well as diagnostic

certainty. TTD can be signicantly shortened by IAC which might lead to

improved patients’ guidance as initial diagnosis carries signicant treat-

ment, prognostic and emotional weight.

Conclusion: IAC can be performed safely and should be implemented

routinely in multidisciplinary spine surgical pathways to improve treat-

ment planning.

Disclosure Statement: e authors declare no conict of interest.

Translational Oncology

Poster

104

Perfusion bioreactor to preserve the microenvironment of ex

vivo hepatocellular carcinoma

Gabriel Fridolin Hess1,2; Mairene Coto-Llerena2,3;

Manuele Giuseppe Muraro2; Caner Ercan2,3; Otto Kollmar1;

Salvatore Piscuoglio2,3; Savas Deniz Soysal1

1Clarunis Viszeralchirurgie, Universitätsspital Basel, Basel, Schweiz

2Departement Biomedizin, Universität Basel und Universitätsspital Basel, Basel,

Schweiz

3Pathologie, Universitätsspital Basel, Basel, Schweiz

Purpose: Hepatocellular carcinoma (HCC) represents an attractive target

for immune checkpoint inhibitors (ICI) and tumor microenvironment

(TME) agents. Patient-derived organoids (PDO) have emerged as models

for ex vivo drug testing. However, the lack of TME and of the immune

cells (IC) hamper their use in the evaluation of ICI and TME-agents. Here,

we developed and characterized a bioreactor-cultivated HCC tissue model

that preserves the tumor tissue architecture and maintains the pathophys-

iological microenvironment of human tissue.

Methods: Tumor fragments of 3mm were installed between two discs of

collagen type 1 scaold and placed in a perfusion bioreactor (U-shaped

Culture Under Perfusion; U-CUP). Cell viability and morphology was

monitored on day 1, 5 and 7. At each time point, fragments were forma-

lin-xed and paran-embedded for downstream analysis. e changes in

TME composition were monitored by immunohistochemistry using cell-

type specic antibodies.

Results: Microscopic analysis revealed that the morphology and the via-

bility of the cells were preserved during the culture period in the U-CUP

at each time point. Tissue histology as well as the immunophenotypic

pattern observed in the original tissue for specic markers such as argi-

nase, was maintained. Endothelial cells and broblasts, identied by the

expression of CD31 and a-SMA, were detected in the U-CUP cultured

samples in a similar proportion to the original tumor samples. e pres-

ence of IC, described by the expression of CD3, was detected at all time

points.

Discussion: Patient-derived organoids from HCC have shown to pre-

serve the genetic characteristic of the tumor, however lacking TME and

IC components. Bioreactor technology has been used in the context of tis-

sue regeneration previously. Compared to the PDO, U-CUP has shown to

preserve mesenchymal and immune components in HCC tissue, allowing

the assessment of TME-related treatments.

Conclusions: U-CUP HCC is a promising option for ex-vivo testing ICI

and TME-agents in HCC.

Disclosure Statement: e authors declare no conict of interest.

199

CAF-associated signaling pathways are linked to platinum

resistance in high-grade serous ovarian carcinoma

Michael Wessolly1; Elena Mairinger1; Sabrina Borchert1; Agnes Bankfalvi1;

Pawel Mach2; Kurt Werner Schmid1; Rainer Kimmig2; Paul Burderath2;

Fabian Dominik Mairinger1

1University Hospital Essen, Institute of Pathology, Essen, Deutschland

2University Hospital Essen, Department of Gynecology and Obstetrics, Essen,

Deutschland

Background: High-grade serous ovarian carcinoma (HGSOC) is the

predominant histological subtype of ovarian cancer diagnosed in clini-

cal settings. It accounts for most cancer-related deaths across all forms

of ovarian cancer. One distinguishing factor, linked to poor prognosis, is

the occurrence of myobroblast cells and extensive desmoplastic stromal

reaction (DSR). Due to frequent acquirement of therapy resistance aer

initial treatment with platinum-based components, we intent to explore

the activity of DSR-associated signaling pathways in HGSOC patients.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 255

Methods: e cohort consists of 24 platinum treated HGSOC patients

with complete clinical follow-up. RNA was isolated from paran-em-

bedded tumor samples. Digital expression analysis of genes involved in

DSR-associated pathways was performed by the NanoString nCounter

platform. Data were explored using the R programming environment

(v.4.0.3).

Result: e expression of MMP13, CGA, EPHA3, PSMD9, PITX2,

PHLIPP1 was linked to chemoresistance. Additionally, 15 genes were

directly associated with patients’ survival, including MMP13 and CGA.

Gene set enrichment analysis revealed dierent pathways linked to resis-

tance. Consistently expressed core components were mostly involved in

growth factor (TGF-ß, Ras, MAPK) as well as PI3K-Akt signaling. ese

ndings could be validated in 303 epithelial ovarian carcinomas.

Discussion: We were able to link DSR-associated pathways, marked by

increased Ras, MAPK and PI3K-Akt signaling to resistance development.

Activation of those pathways seems to be based on non-canonical TGF-ß

signaling and increased activity of cancer-associated broblasts.

Conclusion: Since platinum-based chemotherapy still is the state-of-the-

art therapy to treat HGSOC, reasons for therapy resistance need to be

identied. is work unfolds DSR as one possible contributor. erefore,

it may be helpful to stratify HGSOC patients for DSR and consider alter-

native treatment options.

Disclosure Statement: e authors declare no conict of interest.

243

Human leukocyte antigen (HLA) typing of cancer patient-

derived xenografts (PDX) models enables personalized,

preclinical immune-oncology studies

Theresia Conrad1; Annika Wulf-Goldenberg1; Maria Stecklum1;

Michael Becker1; Simone Rhein1; Konrad Klinghammer2; Jens Homann1

1EPO Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin,

Deutschland

2Charité University Medicine, Berlin, Deutschland

Background: In immuno-oncology research, matching of human leuko-

cyte antigen (HLA) proles of patient-derived xenogras (PDX) and com-

patible human immune cell populations is an important factor to enable

personalized, preclinical studies. With this objective, we determined indi-

vidual HLA proles of a broad panel of PDX models from 18 dierent

tumor entities and performed comprehensive HLA matching analyses of

all models and 14 peripheral blood mononuclear cell (PBMC) donors.

Methods: Based on RNA-sequencing data, HLA class I, II and non-class

types of 291 established PDX models were determined in 4-digit resolu-

tion. For comparative analyses, HLA allele and haplotype frequencies of

8862 German stem cell donors (GSCD) provided by e Allele Frequency

Net Database were used. According to donor-recipient HLA matching cri-

teria recommended by the Blood and Marrow Transplant Clinical Trials

Network, matching analyses of all PDX and 14 PBMC donor HLA proles

were performed.

Result: More than 50 % of the determined individual HLA proles show

allele homozygosity at ≥ 1 HLA class I loci. Comparisons of PDX and

GSCD HLA proles resulted in comparable frequencies of most of the

alleles and haplotypes but also in certain variations. HLA prole match-

ing analyses performed for PBMC donors and PDX models revealed 15

matches including PDX from 9 tumor entities. Exemplarily, the depen-

dence of immune therapy ecacy on matched HLA proles was shown

for a head and neck squamous cell cancer PDX humanized with PBMCs

from the patient and 3 donors.

Discussion: Interestingly, the obtained high proportions of homozygosity

and specic HLA haplotypes were likewise reported in the literature and

may serve as prognostic markers for risk and progression of cancer.

Conclusion: e generated comprehensive HLA prole portfolio contain-

ing matching information on a broad panel of PDX models and PBMC

donors supports the investigation of prognostic markers and enables per-

sonalized, preclinical immune-oncology studies to encourage the devel-

opment of novel immune-therapeutic strategies.

Disclosure Statement: e authors declare the following:

e authors eresia Conrad, Annika Wulf-Goldenberg, Maria Stecklum, Michael

Becker, Simone Rhein and Konrad Klinghammer declare no conict of interest.

Jens Homann declares the employment and the ownership of EPO Berlin-Buch

GmbH.

260

Identication of mechanisms of primary and secondary

resistance to anti-egfr and braf inhibition in brafv600e CRC

PDOS and PDX

Anna Kotarac1,2; Hiroki Osumi3; Manuela Benary4; Arndt Stahler2;

Stephan Hahn5; Sandra Liebs1; Anastasia Dielmann1; Ulrike Krueger6;

Tomasz Zemojtel6; Merve Keziban7,8; Philipp Mertins7,8; Christian Rosé9;

Frank Reichenbach9; Ryoji Yao10; Ulrich Keilholz1; Sebastian Stintzing2;

Loredana Vecchione1,2

1Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,

Berlin, Germany

2Department of Hematology, Oncology, and Cancer Immunology, Campus

Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany

3Department of Gastroenterology, Cancer Institute Hospital, Japanese

Foundation for Cancer Research

4BIH-Core Unit Bioinformatics, Charité - Universitätsmedizin Berlin, Berlin,

Germany

5Zentrum für Klinische Forschung (ZKF) , Ruhr-Universität Bochum, Bochum,

Deutschland

6BIH-Core Unit Genomics, Charité - Universitätsmedizin Berlin, Berlin, Germany

7Berlin Institute of Health (BIH) Core Unit Proteomics, Charité -

Universitätsmedizin Berlin, Berlin, Germany

8Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany

9Pierre Fabre Pharma GmbH, Freiburg, Germany

10Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer

Research, Tokio, Japan

Background: e combination of cetuximab (C225) and encorafenib

(LGX818) is the rst chemo free regimen approved for the treatment

of BRAFV600E mCRC patients (1). Despite of its activity, very little is

known about mechanisms of primary and secondary resistance (2,3,4).

erefore, the aim of the current work is to identify such mechanisms and

potential strategies to overcome resistance.

Methods: Ten BRAFV600E CRC patient-derived organoids (PDOs)

were treated with single agents cetuximab (C225), erlotinib (OSI-774),

encorafenib (LGX818) and irinotecan (SN-38) as well as C225+LGX818,

OSI-774+LGX818, C225+SN38 and OSI-774+SN-38 in the presence

and absence of EGF. All models were proled using whole exome DNA

sequencing, RNAseq and mass spectrometry. Moreover, RNAseq was per-

formed aer 24h of OSI-774+LGX818 in three sensitive and three resis-

tant models. Finally, ten dierent patient-derived xenogras (PDX) were

treated with single agents and combination treatments. PDXs samples

were collected before and upon progression for molecular analysis.

Results: All PDO models showed intrinsic resistance to C225, OSI-

774 and LGX818, independent of the presence of EGF. e response

to SN-38 was more variable. None of the models tested showed sensi-

tivity to C225+LGX818, while 3 out of 10 PDOs were sensitive to OSI-

774+LGX818. e molecular analysis of those models and the PDX

treatments are currently ongoing and will be presented at the conference.

Discussion: While our PDOs showed resistance towards C225, drug com-

binations with OSI-774 resulted in variable responses. e full molecu-

lar characterization of these models should help in identifying genomic

determinants of good and poor response to these treatments.

Conclusions: To the best of our knowledge, this is the rst preclinical study

using PDO and PDX models aiming to identify mechanisms of primary

and secondary resistance to the combination of anti-EGFR+LGX818.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts256

References:

1. Tabernero J et al, PMID:33503393

2. Oddo D et al, PMID:27312529

3. Middleton G et al, PMID:32047001

4. Huiberts SCFA et al, PMID:33204026

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

388

Molecular mechanisms of colorectal cancer: MACC1 and the

novel IER2 gene

Miguel Alberto1,2,3; Lenka Kyjacova4; Marc Osterland2,3;

JonathanSleeman5,6; Beate Rau1; Ulrike Stein2,3

1Charité - Universitätsmedzin Berlin, Surgical Department, Berlin, Deutschland

2Charité - Universitätsmedzin Berlin, Experimental and Clinical Research Center,

Berlin, Deutschland

3Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland

4University of Heidelberg, Medical Faculty Mannheim, Mannheim, Deutschland

5University of Heidelberg, Medical Faculty Mannheim, European Center for

Angioscience, Mannheim, Deutschland

6Karlsruher Institute for Technology, IBCS-BIP, Eggenstein-Leopoldshafen,

Deutschland

Background: e gene Metastasis Associated in Colon Cancer-1

(MACC1) is a key player for metastasis formation, tumor progression

and is a biomarker for CRC and more than 20 other solid cancer types.

Higher MACC1 expression is associated with metachronous metastasis.

Immediate Early Response 2 (IER2) is a novel player in the eld of metas-

tasis. Previous studies have linked IER2 expression with enhanced meta-

static capacities contributing to worse overall survival.

Methods: We analyzed in-silico mRNA expression proles and predictive

binding motifs for MACC1 and IER2. We made use of qRT-PCR, Western

Blot, clonogenic and proliferation assays. Furthermore, we used CRISPR-

Cas9 for creation of an IER2 knockout cell line.

Result: Cumulative survival for patients with higher expression of IER2

and MACC1 genes was signicantly worse. In-silico, both a positive

correlation between MACC1 and IER2 expression and a predicted SH3

mediated protein interaction was found. Overexpression of IER2 warrants

higher in vitro colony forming capabilities and silencing IER2 signi-

cantly hinders cellular proliferation.

Discussion: Both genes share similar roles in conferring the cell aggressive

metastatic capabilities. is synergism could be due to a SH3-mediated

protein interaction. MACC1 is a key regulator of a

HGF/cMET-mediated pro metastatic axis. IER2 is involved in CDC25A

dysregulation enhancing G1-S transitions,1 hence the heightened clono-

genic traits of the cell. Furthermore, PP2A´s substrate specicity may be

directly inuenced by IER2.1

Conclusion: MACC1, an established marker for metastatic disease and

IER2, a novel biomarker, may play an important synergetic role to con-

fer cancer cells enhanced proliferative and clone formation attributes.

e synergism between them undeniably translates into worst patient

outcomes.

Indication of source:

1. Ueda, T. et al. IER family proteins are regulators of protein phosphatase PP2A

and modulate the phosphorylation status of CDC25A. Cell. Signal. 55, 81–89

(2019).

Disclosure Statement: e authors declare no conict of interest.

405

Characterization of a novel lipase inhibitor targeting high

cancer stemness in triple-negative breast cancer (TNBC)

Hannah Grundmann1; Theresa Bozzetti1; Jasmin On1; Andrea Kulik1;

Dieter Niederacher1; Hans Neubauer1; Tanja Fehm1; Knud Esser1

1Heinrich-Heine-Universität Düsseldorf, Life Science Center, Forschungslabore

der Klinik für Frauenheilkunde und Geburtshilfe, Düsseldorf, Deutschland

Background: High cancer stemness is a main driver of TNBC malig-

nancy. However, to date the underlying pathophysiology is only partially

understood. Recently, dysregulated lipid metabolism has been suggested

to mainly contribute to TNBC stemness maintenance and pharmacolog-

ical interference with tumor cell lipid metabolism has been reported as a

promising strategy to improve cancer therapy.

Methods: We analyzed an in-house library of 2.000 compounds includ-

ing metabolically active agents by a cell-based phenotypic high-through-

put screening system to identify potentially cancer stemness reducing

agents. Reduction of cancer stem cell marker expression was quantied

by measuring the expression levels of two innovative dierentiation

markers, followed by validation with qRT-PCR and ow cytometry anal-

ysis. Furthermore, increased sensitization to treatment with Paclitaxel

and Doxorubicin was investigated by co-incubation. MDA-MB-231 and

MDA-MB-436 cells were used as in vitro model. To scrutinize lipase

expression in primary breast cancer tissue bioinformatic databases were

used.

Result: We identied a selective lipase inhibitor that specically reduced

TNBC stemness and increased sensitivity to chemotherapies. Besides

expression of the candidate lipase strongly correlated with cancer stem

cell marker expression in primary breast cancer.

Discussion: e identied lipase is highly expressed in TNBC cancer

stem cells and its activity plays an essential role in maintaining the high

cancer stem cell character of TNBC cells.

Conclusion: Pharmacological inhibition of the identied lipase may rep-

resent a new therapeutic approach for TNBC treatment and could improve

current cancer therapy due to its specic reduction of TNBC stemness.

Disclosure Statement: e authors declare no conict of interest.

416

Signaling pathways linked to activity of cancer-associated

broblasts lead to cancer progression and increased tumor

cell motility in malignant pleural mesothelioma

Michael Wessolly1; Alexander Mathilakathu1; Elena Mairinger1;

Alina Nath1; Henrik Beckert2; Daniel Kreidt1; Nick Klopp1; Balazs Hegedüs3;

Julia Steinborn1; Thomas Hager4; Robert Fred Henry Walter1;

Daniel Christian Christoph5; Jens Kollmeier6; Jeremias Wohlschlaeger4;

Thomas Mairinger7; Luca Brcic8; Sabrina Borchert1; Kurt Werner Schmid1;

Fabian Dominik Mairinger1

1University Hospital Essen, Institute of Pathology, Essen, Deutschland

2University Hospital Essen, Ruhrlandklinik-West German Lung Centre, Clinic of

Pulmonology, Division of Translational Pulmonology, Essen, Deutschland

3University Hospital Essen, Ruhrlandklinik-West German Lung Centre,

Department of Thoracic Surgery and Thoracical Endoscopy, Essen, Deutschland

4Diakonissenkrankenhaus Flensburg, Department of Pathology, Flensburg,

Deutschland

5Evangelische Huyssens Foundation Essen-Huttrop, Department of Medical

Oncology/Hematology, Essen, Deutschland

6Helios Klinikum Emil von Behring, Lungenklinik Heckeshorn, Department of

Pneumonology, Berlin, Deutschland

7Helios Klinikum Emil von Behring, Department of Tissue Diagnostics, Berlin,

Deutschland

8Medical University of Graz, Diagnostic and Research Intitute of Pathology, Graz,

Österreich

Background: Malignant pleural mesothelioma (MPM) is an aggressive,

asbestos-associated malignancy. Oen discovered in advanced tumor

stages, median survival ranges only from 9 to 15 months aer initial diag-

nosis. Unfortunately, long-term therapy responses remain unsatisfying.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 257

In recent years, research focus has shied towards the tumor microen-

vironment (TME) and its contribution to tumor development. Cancer-

associated broblasts (CAFs) are key factors within TME and are known

to exert tumor-proliferative eects. Within this study, we analysed CAF-

mediated eects on MPM cells’ behavior and activity.

Methods: MPM cell lines were subjected to conditioned medium (CM)

from activated myobroblast cell lines and vice versa. Cell viability, necro-

sis, and apoptosis rates were estimated via enzyme-activity. Cell migration

and invasion assays were used to determine tumor cells’ invasive capa-

bilities. Digital gene expression analysis was performed via NanoString

nCounter platform using a panel covering 76 CAF-associated genes.

ese in vitro generated results were veried in a clinical cohort consist-

ing of 77 MPM patients.

Result: Treated mesothelioma cells showed signs of increased invasive

capabilities, cell viability, and proliferation. KEGG pathway analysis

suggested cell cycle progression. Additionally, PI3K-Akt, MAPK, and

Ras pathways appeared highly activated. TGF-ß signaling only showed

upstream activity.

Discussion: While ligands of the TGF-ß signaling pathway were present,

SMAD signaling was inactive. Instead, it seemed that broblast CM treat-

ment enhanced non-canonical TGF-ß signaling via MAPK, PI3K-Akt and

Ras signaling.

Conclusion: e above-mentioned pathways are linked to desmoplastic

stromal reaction (DSR), a progress associated with aggressive tumor sub-

types and therapy resistance. With CAFs being key players of DSR, this

work highlights their tumor-supportive eect in vitro as well as in a clini-

cal cohort, thereby also unveiling potential therapeutic targets.

Disclosure Statement: e authors declare no conict of interest.

524

Peritoneal metastasis of colorectal cancer (pmCRC):

Identication of predictive molecular signatures by a novel

preclinical platform of matching pmCRC PDX/PD3D models

Mathias Dahlmann1,2; Guido Gambara2,3; Bernadette Brzezicha4;

Oliver Popp5; Eva Pachmayr6; Lena Wedeken7; Alina Paume7;

Margarita Mokritzkij1; Safak Gül-Klein6; Andreas Brandl6;

Caroline Schweiger-Eisbacher3; Philipp Mertins5; Jens Homann4;

Ulrich Keilholz2,3; Wolfgang Walther1; Christian Regenbrecht7,8; Beate Rau6;

Ulrike Stein1,2

1Charité - University Medicine Berlin, and Max-Delbrück-Center for Molecular

Medicine in the Helmholtz Association, Experimental and Clinical Research

Center, Translational Oncology of Solid Tumors, Berlin, Deutschland

2German Cancer Consortium, Heidelberg, Deutschland

3Charité – Universitätsmedizin Berlin, Charité Comprehensive Cancer Center,

Berlin, Deutschland

4EPO GmbH Berlin-Buch, Berlin, Deutschland

5Max-Delbrück-Center for Molecular Medicine and Berlin Institute of Health,

Proteomics Platform, Berlin, Deutschland

6Charité - University Medicine Berlin, Department of Surgery, Berlin,

Deutschland

7CELLphenomics GmbH, Berlin, Deutschland

8University Medicine Göttingen, Institute of Pathology, Göttingen, Deutschland

Background: Peritoneal metastasis of colorectal carcinoma (pmCRC)

occurs in approximately 15% of CRC patients, behaves clinically distinct

from hematogenous spread. Predictive molecular signatures to medi-

cal treatments have not yet been dened. e aim of the study was the

establishment and characterization of matched patient-derived xenogra

(PDX) and patient-derived 3D cell culture (PD3D) models from surgical

samples of pmCRC patients for individualized therapy concept to improve

outcome of pmCRC patients and to dene signatures to better guide ther-

apy selection.

Methods: pmCRC metastases were obtained during routine surgery

and used to generate matched PDX/PD3D models, which were treated

with Standard-of-Care (SoC) regimen and targeted drugs, while growth

response was monitored. All sample types were molecularly characterized

by multi-omics technologies to identify putative predictive biomarkers.

Result: 14 pmCRC PDX models, including 9 matched PD3D/PDX mod-

els were established. Preclinical treatment response to 17 SoC and targeted

therapies were integrated with multi-omics data and resulted in predic-

tive biomarkers for 10 treatment options. Of note, enrichment of BRCA2

mutations in the pmCRC samples pointed to the use of PARP inhibitors

as novel two-hit combination therapy, in which combination of olapa-

rib with 5-FU or trametinib strongly improved the response of our PDX

models resistant to respective monotherapy.

Discussion: Patterns of gene/protein expression, coding mutations, and

protein phosphorylation of pmCRC metastases and their derived PD3D/

PDX models correlated well. Data integration revealed altered cellular

processes and signaling pathways impacting therapy response as basis to

molecularly tailor new therapies.

Conclusion: e novel preclinical drug testing platform of matched

pmCRC models, characterized by multi-omics, facilitated the identica-

tion of predictive biomarkers and cancer relevant signatures for ecient

and novel drug combinations to improve the outcome in pmCRC therapy,

ready for validation in clinical cohorts.

Reference:

Dahlmann et al., Mol Cancer, accepted September 2021

Disclosure Statement: e authors declare no conict of interest.

537

The CCCMLMU Molecular Tumorboard: clinical and molecular

characteristics of the rst 1000 patients

Kathrin Heinrich1,2; Lisa Miller-Phillips1,2; Frank Ziemann1,2;

Korbinian Hasselmann1; Katharina Rühlmann2;

Michael von Bergwelt-Baildon1,2; Julian Holch1,2; Tobias Herold1,2,3;

Louisa von Baumgarten2,4; Philipp Greif1,2,3; Irmela Jeremias3,5;

Fabian Trillsch2,6; Rachel Würstlein2,6,7; Andreas Jung2,8; Thomas Kirchner2,8;

Frederick Klauschen3,8,9; Klaus Metzeler10,11; Volker Heinemann1,3,9;

Benedikt Westphalen1,3,9

1Medizinische Klinik und Poliklinik III, LMU Klinikum München, München,

Deutschland

2Comprehensive Cancer Center, LMU Klinikum München, München,

Deutschland

3German Cancer Consortium (DKTK), Partner Site Munich, München,

Deutschland

4Neurologische Klinik und Poliklinik, LMU Klinikum München, München,

Deutschland

5Department of Apoptosis in Hematopoietic Stem Cells, Helmholtz Center

Munich, German Center for Environmental Health (HMGU), München,

Deutschland

6Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum

München, München, Deutschland

7Brustzentrum, LMU Klinikum München, München, Deutschland

8Pathologisches Institut, Ludwig-Maximilians-Universität München, München,

Deutschland

9Comprehensive Cancer Center (CCC), LMU Klinikum München, München,

Deutschland

10Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie,

Universitätsklinikum Leipzig, Leipzig, Deutschland

11German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

Purpose: In 2016, the University of Munich Molecular Tumor Board

(MTB) was implemented to initiate a precision oncology program. is

review of cases was conducted to assess clinical implications and func-

tionality of the program, to identify current limitations and to inform

future directions of these eorts.

Methods: Charts, molecular proles and tumor board decisions of the

rst consecutive 1000 cases (01/2016 – 03/2020) were reviewed.

Results: Of the rst 1000 patients presented to the MTB, 914 patients

received comprehensive genomic proling (CGP). Median age of patients

was 56 years and 58% were female. Patients with 90 dierent malignan-

cies were enrolled in the program. e most prevalent diagnoses were

breast (16%) and colorectal cancer (10%). Dierent types of gene panels

have been used; most of them available through the local department of

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts258

pathology. Testing was technically successful in 88%. In 41% of cases, an

alteration triggered a therapeutic recommendation. e most frequent

actionable alterations were: FGFR alterations (8%), tumour mutational

burden (TMB - 7%) and MET alterations (6%). e most frequent non-ac-

tionable alterations were KRAS (%) and TP53 (%). Frequency of therapy

recommendations diered signicantly in between malignancies ranging

from over 50% in breast or biliary tract cancer to less than 30% in pancre-

atic cancer. Based on this chart review, 17% of patients received treatment

based on the MTB recommendation.

Discussion and Conclusions: e University of Munich precision oncol-

ogy program serves as a clinical platform for caregivers from a variety

of departments. Based on these results, patients with certain malignan-

cies (breast and biliary tract cancer) tend to derive more benet from

enrolment in a precision oncology program. e low rate of just 17%

therapeutic implementation of MTB recommendations underscores the

importance of optimizing the clinical use of CGP. Access to targeted ther-

apies outside of clinical trials and patient selection remain major obstacles

in precision oncology.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

561

Assessing the residual activity of germ-line BRCA2 mutations

by novel malignancy risk prediction score

Ivana Radulovic1, Michael Schündeln1, Lisa Müller2, Johannes Ptok2,

Ellen Honisch3, Dieter Niederacher3, Heiner Schaal2, Constanze Wiek4,

Helmut Hanenberg1 4

1Department of Pediatrics III, University Hospital Essen, University of Duisburg-

Essen, Essen, Deutschland

2Institute of Virology, University Hospital Düsseldorf, Heinrich Heine University

Duesseldorf, Duesseldorf, Deutschland

3Department of Gynecology and Obstetrics, University Hospital Düsseldorf,

Heinrich-Heine University Düsseldorf, Düsseldorf, Deutschland

4Department of Otorhinolaryngology & Head/Neck Surgery, University Hospital

Düsseldorf, Heinrich Heine University, Düsseldorf, Deutschland

Background: BRCA2 is an essential DNA repair gene that is frequently

mutated in pedigrees with breast, ovarian and pancreatic cancers. Bi-allelic

germ-line mutations in BRCA2 occur in a rare pediatric inherited disor-

der, Fanconi anemia (FA) subtype FA-D1, that is clinically characterized

by congenital abnormalities and an extremely high propensity to develop

malignancies. As no living organism with a complete loss of BRCA2 pro-

tein function exists, we hypothesized that the clinical manifestation of

malignancies in these children can be used to assess residual function(s)

of mutated BRCA2 allels.

Methods: To develop an algorithm predicting the clinical phenotype of

BRCA2 mutations, data from published FA-D1 patients with bi-allelic

BRCA2 mutations were used in a novel scoring system: alleles with frame-

shi/stop codon mutations were assigned 0 and with missense mutations

+1 points. Alleles with mutations downstream of exon 11 received +1.

e MaxEnt and HBond splicing scores were used to assign 0 points to a

severe and +1 to a mild splice disturbation. Points from both alleles were

then correlated with dierent clinical parameters of the malignancies.

Result: 70 FA-D1 patients had a lifetime cancer risk of 92.9% with 1-4

malignancies. We could distinguish 3 risk groups (scores: 0, 1, >1), with

median ages of cancer of 1.3, 3.05 and 4.9 years, associated with median

OS of 2.3, 4.9 and 17.0 years, respectively.

Discussion: Our algorithm predicts residual functions of mutated BRCA2

alleles in humans, strongly inuencing the manifestation of malignancies.

Conclusion: To validate the algorith, the scores/mutations should be

correlated with cancer manifestations of heterozygous germ-line BRCA2

carriers and mutant proteins experimentally tested in engineered human

FA-D1 cells.

Disclosure Statement: e authors declare no conict of interest.

563

Mapk inhibition in combination with vinorelbine might

represent a new therapeutical option for brafv600e CRC

Anna Kotarac1,2; Hiroki Osumi3; Sandra Liebs1; Anastasia Dielmann1;

Ryoji Yao4; Ulrich Keilholz1; Sebastian Stintzing2; Loredana Vecchione1,2

1Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,

Berlin, Germany

2Department of Hematology, Oncology, and Cancer Immunology, Campus

Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany

3Department of Gastroenterology, Cancer Institute Hospital, Japanese

Foundation for Cancer Research, Tokio, Japan

4Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer

Research, Tokio, Japan

Background: BRAFV600E colon cancer (CRC) cell lines were observed

to be extremely sensitive to vinorelbine (VBN) (1). A subsequent phase

II study could not conrm these results (2). e multidrug resistant phe-

notype, driven by the expression of P-glycoprotein and regulated by the

mitogen activated protein kinases (MAPK) pathway (3), is a well-known

intrinsic mechanism of VBN resistance and could have resulted in the

negative phase II study. Here, we investigated if combining VBN with

anti-Epidermal Growth Factor Receptor (EGFR) together with MAPK

inhibitors increases its activity in CRC cell lines and patient derived

Organoids (PDOs).

Methods: ree BRAFV600E CRC cell lines were treated with VBN

alone or in combination with cetuximab (C225) + encorafenib (LGX818).

Moreover, ten BRAFV600E CRC PDOs were treated with single agent

VBN; PDOs with higher VBN IC50 were treated with VBN in combina-

tion with erlotinib (OSI-774) + LGX818.e expression of pEGFR, pAKT,

pERK, P-glycoprotein and cleaved PARP was tested both in cell lines and

PDOs aer 24, 48, and 72h.

Results: e addition of C225+LGX818 to VBN resulted in a signicantly

lower IC50 (13.7-17,500-fold change) than VBN alone in all tested CRC cell

lines. All PDOs were sensitive to VBN alone. Treating the two PDOs with

highest VBN IC50 with the triple combination of VBN+OSI-774+LGX818

resulted in a signicantly lower IC50 (6-180-fold change) than VBN

alone. Treatment with MAPK inhibitors reduced P-glycoprotein expres-

sion already aer 24 h. e addition of C225+LGX818 to VBN showed a

signicant increase of cleaved PARP as compared to C225+LGX818 and

VBN alone. Similar results were obtained in PDOs.

Discussion: e addition of C225+LGX818 to VBN signicantly

increased the activity of VBN in both BRAFV600E CRC cell lines and

PDOs. is phenotype is due to the P-glycoprotein reduction through the

MAPK pathway inhibition.

Conclusions: e triple combination represents a promising treatment

option for BRAFV600E mCRC patients.

References:

1. Vecchione L et al PMID:27058664

2. Cremolini C et al PMID:29209533

3. Katayama K. et al PMID:17620438

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

603

Larger ectosome-like EVs mirror the pattern of surface

markers on malignant cells: a cell line-based study

Hari Gorantla1; Vijay Boddu2; Nikolas von Bubno2; Frank Gieseler2

1UKSH Campus Lübeck, Klinik für Hämatologie und Onkologie, Molekulare

Therapie, Lübeck, Deutschland

2Klinik für Hämatologie und Onkologie, UKSH Campus Lübeck, Lübeck,

Deutschland

e presence of reliable biomarkers in the diagnosis and treatment of

malignant diseases is a long-held wish for oncologists, especially in the

treatment of solid tumors, where histological biopsies might be necessary

otherwise. As we learn more about the genetic characteristics, the proof

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 259

of the corresponding mutations in tumor cell-derived genetic material

found in the plasma and in extracellular vesicles (EVs) is a promising way.

During the preparation and enrichment of smaller exosome-like EVs for

the analysis of incorporated genetic material, the larger ectosome-like ves-

icles are regularly discarded aer the high-speed centrifugation step. We

and others think that this is a waste of valuable biological material for at

least two reasons: (1) the preparation of larger ectosomes is, due to their

bigger size, more specic and (2) due to their biogenesis by blebbing of

the outer membrane ectosomes might mirror the membrane components

of the parental cell.

In this project, we examined potentially biological relevant surface

markers of leukemia cell lines, having known genetic mutations, as well as

two bladder cancer cell lines with dierent biological properties (muscle

invasive and non-invasive), and compared them with their correspondent

larger ectosome-like EVs. We found, (1) that the preparation of larger

ectosome-like EVs by sequential centrifugation is highly specic, and

(2) that ectosomes indeed reect and mirror the membrane markers of

their parental cells in many cases. Although this is an in-vitro study using

cell lines, we think that the results are noteworthy and might serve as a

proof-of-principles study, as we show that larger ectosome-like EVs can be

prepared with high selectivity using the described methods, and that they

might be used as surrogate markers in biomaterial from patients, such

as blood or urine. Further studies might show the functional relevance,

e.g. for the forming of the tumor micro-environment by EVs released by

malignant cells.

Disclosure Statement: e authors declare no conict of interest.

605

MEK1 mediated essential tyrosine phosphorylation of MACC1

is druggable to eciently restrict colorectal cancer metastasis

Dennis Kobelt1,2; Daniel Perez-Hernandez3,4; Claudia Fleuter1;

Mathias Dahlmann1,2; Fabian Zincke1; Janice Smith1; Rebekka Migotti3;

Oliver Popp3; Susen Burock5; Wolfgang Walther1; Gunnar Dittmar3,4;

Philipp Mertins3; Ulrike Stein1,2

1Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin

and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association,

Translational Oncology of Solid Tumors, Berlin, Deutschland

2German Cancer Consortium (DKTK), Heidelberg, Deutschland

3Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association,

Mass Spectrometry Core Unit, Berlin, Deutschland

4Luxembourg Institute of Health, Proteome and Genome Research Laboratory,

Strassen, Luxemburg

5Charité - Universitätsmedizin Berlin, Charité Comprehensive Cancer Center,

Berlin, Deutschland

Background: Cancer metastasis causes >90% of cancer deaths and

remains a major treatment challenge. We deciphered the impact of tyro-

sine phosphorylation of MACC1, a causative driver for cancer metas-

tasis, for cancer cell signaling and novel interventions to restrict cancer

metastasis.

Methods: e MEK1/MACC1 axis was identied by mass spectrometry

(MS). MACC1 tyrosine phosphorylation sites were identied by in sil-

ico predictions, and validated by quantitative SRM-MS and site-directed

mutagenesis. MEK1 phosphorylation of MACC1 was functionally tested

in vitro and in mice regarding CRC cell motility, proliferation and metas-

tasis, and in human CRC specimens.

Result: We identied MACC1 as new MEK1 substrate. MEK1 directly

phosphorylates MACC1, leading to accelerated and increased ERK1 acti-

vation. Mutating in silico predicted hierarchical MACC1 tyrosine phos-

phorylation sites abrogates MACC1-induced migration, invasion and MET

expression, a transcriptional MACC1 target. Targeting MEK1 by RNAi or

clinically applicable MEK1 inhibitors AZD6244 and GSK1120212 reduces

MACC1 tyrosine phosphorylation and restricts MACC1-induced metas-

tasis formation in mice. Although MEK1 levels, contrary to MACC1, are

not of prognostic relevance for CRC patients, MEK1 expression was found

indispensable for MACC1-induced metastasis.

Discussion: is study identies MACC1 as new MEK1 substrate for

tyrosine phosphorylation decisively impacting cell motility, tumor growth

and metastasis. us, MAP kinase signaling is not linear leading to ERK

activation, but branches at the level of MEK1. is fundamental nding

opens new therapeutic options for targeting the MEK1/MACC1 axis as

novel vulnerability in patients at high risk for metastasis.

Conclusion: e ndings shown for CRC might be translated to further

solid tumor types. e usefulness of MACC1 as therapeutic target towards

MEK1 inhibitor treatment requires conrmation in clinical trials.

Indication of source:

1 Oncogene. 2021 Aug;40(34):5286-5301.

Disclosure Statement: e authors declare no conict of interest.

622

Cancer-associated broblasts regulate kinase activity in

mesothelioma cell lines via paracrine signaling and thereby

dictate cell faith and behavior

Fabian Dominik Mairinger1; Alexander Mathilakathu1; Michael Wessolly1;

Elena Mairinger1; Hendrik Beckert2; Daniel Kreidt1; Luka Brcic3;

Julia Steinborn1; Kristina Greimelmaier4; Jeremias Wohlschlaeger4;

Kurt Werner Schmid1; Sabrina Borchert1

1Institute of Pathology, University Hospital Essen, Deutschland

2Department of Pulmonary Medicine, University Hospital Essen, Essen,

Deutschland

3Diagnostic and Research Institute of Pathology, Medical University of Graz,

Graz, Österreich

4Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,

Deutschland

Background: Malignant pleural mesothelioma (MPM) is a rare type of

cancer with an infaust prognosis despite multimodal therapy. MPM cells

modulate the immune response to their benet. ey release proinam-

matory cytokines, such as TGF-ß, awakening resting brocytes that switch

their phenotype into activated broblasts. Signaling interactions between

cancer cells and cancer-associated broblasts (CAFs) play an integral part

in tumor progression. is study aimed to investigate the role CAFs play

in MPM progression, analyzing the impact this complex, symbiotic inter-

action has on kinase-related cell signaling in vitro.

Methods: We simulated paracrine signaling in vitro by treating MPM

cell lines with conditioned medium (CM) from broblasts (FB) and vice

versa. NCI-H2052, MSTO-211H, and NCI-H2452 cell lines representing

the three mayor MPM subtypes, while embryonal myobroblast cell lines,

IMR-90 and MRC-5, providing a CAFs-like phenotype. Subsequently,

dierences in proliferation rates, migratory behavior, apoptosis, necrosis,

and viability were used as a covariate for data analysis. Kinase activity of

treated samples and corresponding controls were then analyzed using the

PamStation12 platform (PamGene).

Result: Treatment with myobroblast-derived CM revealed signicant

changes in phosphorylation patterns in MPM cell lines. e observed

eect diers strongly between the analyzed MPM cell lines and depends

on the origin of CM. Overall, a much stronger eect was observed using

CM derived from IMR-90 than MRC-5. e phosphorylation changes

mainly aected the MAPK signaling pathway.

Discussion: e factors secreted by myobroblasts in broblasts CM sig-

nicantly inuence the phosphorylation of kinases, mainly aecting the

MAPK signaling cascade in tested MPM cell lines.

Conclusion: Based on our in vitro results, the use of MEK or ERK inhibi-

tors could have a positive synergistic eect with cisplatin-based treatment,

potentially improving clinical outcomes for MPM patients.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts260

684

Co-culture of patient-derived tumor organoids with

autologous immune cells for therapy response prediction

Alina Paume1; Samantha Exner1; Jürgen Loskutov1;

Christoph Reinhard1,2; Christian Regenbrecht1,2,3

1CELLphenomics GmbH, Berlin, Deutschland

2ASC Oncology GmbH, Berlin, Deutschland

3University Hospital Göttingen, Department for Pathology, Göttingen,

Deutschland

Background: Cancer research is increasingly focusing on immunother-

apies such as immune checkpoint inhibitors that activate the patient’s

immune system by PD-L1 or CTLA-4 inhibition to specically target the

tumor. is requires appropriate and clinically relevant in vitro tumor

models to assess the eciency of these novel drugs not only for preclinical

drug development, but for therapy prediction on the individual patient’s

level.

Methods: Autologous PBMCs were co-cultured with corresponding 3D

patient-derived tumor organoids in presence or absence of additional

immune checkpoint inhibitors such as Nivolumab, Pembrolizumab or

Ipilimumab. eir interaction and the inuence on tumor cell viability

and apoptosis was investigated by proliferation and FACS analysis.

Results: We developed a short-term co-culture assay and applied it to 10

dierent models of dierent entities including melanoma, colon cancer

and sarcoma. Analysis of the basal PBMC viability revealed diverging pat-

terns of activation or suppression, which could be modulated by addition

of immune checkpoint inhibitors.

Discussion: Our assay aims at representing the tumoral and immunolog-

ical characteristics of the patient using autologous 3D co-culture models

without additional immune cell stimulation. e focus lies on a straight-

forward workow, the results of which can be easily integrated into the

overall clinical picture and the subsequent therapeutic decision. In addi-

tion, deeper tumor expression analyses of MHC I/II, PD-L1 and CTLA-4

is necessary for a better understanding of tumor evasion and development

of eective counter strategies.

Conclusions: Further development of patient-specic co-culture screen-

ing approaches is essential for immune therapy prediction. In that way,

responders could be selected from non-responders in advance, treatment

responses improved, and valuable time and costs saved.

Disclosure Statement: e authors declare the following:

Christian Regenbrecht is shareholder at CELLphenomics GmbH, a company

oering drug screens on organoid models, and ASC Oncology GmbH, a company

involved in patient specic therapy prediction. Christoph Reinhard is shareholder

at ASC Oncology GmbH.

711

TP53-dependent release of extracellular vesicles (EVs) from

urological malignancies aects functional status of tumor

associated macrophages and therapy response

Barbara Köditz1, Elena Izquierdo2, Tim Nestler1, Michael Hallek2,

AxelHeidenreich1, Melanie von Brandenstein1, Christian Pallasch2

1Uniklinik Köln, Urologie, Köln, Deutschland

2Uniklinik Köln, Innere Medizin I, Köln, Deutschland

Background: Immune evasion is one of the hallmarks of cancer and one

of the most important strategies for tumor survival. One mediator, which

can induce immune evasion and therefore tumor survival, are extracellu-

lar vesicles (EVs). EVs can be secreted by tumor cells and are “mini-maps”

of the secreting cell. Here the question was if EVs derived from tumor cells

with dierent TP53 status can have an impact on macrophage activation

and therefore on phagocytosis of tumor cells.

Methods: EVs from two prostate cancers (PC3 and LNCap), bladder car-

cinoma (HTB-9) and seminoma (TCam2) were investigated. e impact

of EVs on phagocytosis was analyzed by an antibody dependent cellu-

lar phagocytosis (ADCP). In order to understand the role of PD-L1 and

CD47 in this mechanism, EVs were pretreated with Anti-PD-L1 and

Anti-CD48 and further investigated in an ADCP. To proof the principle of

the role between EVs and PD-L1, CRISPR-KO of PD-L1 and RAB27A in

PC3 cells were established and isolated EVs analyzed via an ADCP.

Result: EVs derived from cancer cells with dierent TP53 status can have

an impact on macrophage activation and therefore on phagocytosis of

tumor cells. EVs derived from TP53 null cell line (PC3) cause a signi-

cant decrease of phagocytosis, compared to TP53 wild type (LNCap and

Tcam2) and to the control. To investigate the role PD-L1 and CD47 were

blocked on the EVs. In the case of blockage of PD-L1 on PC3 derived EVs

cause signicant increase on phagocytosis performed by macrophages.

Furthermore the blockage of PD-L1 and Rab27A in PC3 cells cause a sig-

nicant increase in macrophage activation.

Discussion: Based on the results, it could be seen, that EVS has an impact

on macrophage activation and therefore on the phagocytosis of tumor

cells. On the other hand, also the p53 status of the tumor cell seem to have

an impact.

Conclusion: It could be concluded that EVs derived from tumor cells with

dierent TP53 status can have an impact on macrophage activation in the

presence of exosomal PD-L1 and therefore on the therapy response.

Disclosure Statement: e authors declare no conict of interest.

715

Novel Androgen receptor truncation in Cologne collective

Melanie von Brandenstein; Manuel Huerta; Ermila Spahic;

BarbaraKoeditz; Sina Wagner; Axel Heidenreich

University Hospital of Cologne, Clinic and Polyclinic for Urology, Cologne,

Deutschland

Background: e HSD3B1 SNP at position 1245 is responsible for

resistance to androgen-deprivation therapy (ADT) in prostate cancer.

According to the literature it seems, that not only the mutation is respon-

sible for resistance to ADT in prostate cancer. A further possible expla-

nation of failed ADT can be a truncation or mutation of the androgen

receptor (AR). Several dierent mutations of the AR are already known,

nevertheless, we identied a novel truncated AR, called AR/TC. It was

possible to identify a hypothetical miR/DNA binding site.

Methods: We isolated the cfRNA from blood (n=90) and performed SNP

PCR and qRT-PCR for the identication of the novel truncated AR. We

analyzed our collective on the presences and distribution of heterozygotes

vs homozygotes (n=50). erefore, we isolated the cfDNA from blood

samples and established a SNP PCR. Since the hypothesized truncation

of the AR is only present on RNA level, we isolated the RNA form blood

and performed qRT-PCR.

Result: e distribution of heterozygotes to homozygotes was 50%. Even

in our group of castration-resistant PCa there was a distribution of 50%.

Furthermore, the novel truncated AR was present in all patients in the

group of castration-resistance. Signicant dierences were detectable by

comparing the group of castration-resistance patients with patients who

were diagnosed with high risk or intermediate prostate cancer.

Discussion: According to the identication of a novel truncated AR fur-

ther experiments needed.

Conclusion: It seems to be of great importance to screen all patients

regarding the HSD3B1 mutation. Whether the newly identied AR/TC

is responsible for castration-resistance or whether the ADT increases the

miR and therefore leads to an overproduction of the AR/TC needs to be

proven in detail.

Disclosure Statement: e authors declare no conict of interest.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 261

740

Single Cell RNA Sequencing Workow for Circulating Tumor

Cells in Metastatic Breast Cancer Research

Anna Abramova; André Franken; Mahdi Rivandi; Liwen Yang;

EllenHonisch; Dieter Niederacher; Tanja Fehm; Hans Neubauer

Department of Obstetrics and Gynecology, University Hospital and Medical

Faculty of the Heinrich-Heine-University Duesseldorf, Düsseldorf, Deutschland

Background: Circulating tumor cells (CTCs) can act as an analyte of a

non-invasive liquid biopsy. Despite their rare presence in the cancer

patients’ blood their potential as a prognostic and predictive biomarker

forces the medical research to establish sensitive methods for clinical anal-

ysis. In this context, we have implemented a single cell RNA sequencing

workow on breast cancer (BC) cell line cells adapted to conditions of

CTCs.

Methods: Non-xed BC cell line cells (luminal MCF7 and triple-nega-

tive MDA-MB-231) were spiked into healthy donors’ blood samples and

enriched with the CellSearch system followed by suspension staining

using an antibody cocktail against EpCAM, MUC1, HER2/neu, and CD45

as well as the dye Annexin V to detect early apoptotic cells. Single cells

were picked with the CellCelector system followed by library preparation

using the QIAseq UPX 3‘ Transcriptome Kit. Sequencing was performed

on the MiSeq system.

Result: e use of an EpCAM, MUC1 and HER2/neu antibody cocktail

increased the identication rate of CTCs from patients with luminal BC

compared to each antibody alone. e additional discrimination of early

apoptotic cells by Annexin V improved the quality of selected single cells,

which was mirrored by a 16-fold RNA yield and increased transcript

diversity as well as higher read numbers and the presence of mapped reads

for ACTB and GAPDH. By comparing MCF7 and MDA-MB-231 cells, we

were able to dierentiate both cell lines on single cell level and observed

the expected dierences in the expression of e.g. EPCAM, KRT8/18/19,

CD24, VIM, ADAM8/19, ANKRD1, and AXL. Spiking MCF7 cells into

healthy donors’ blood samples and processing with our workow did not

impair the data quality compared to non-processed cells (R = 0.8).

Conclusion: We implemented a single cell RNA sequencing workow

including careful preanalytical detection of high-quality cells, which will

strongly improve CTC analysis for a clinical setting.

Disclosure Statement: e authors declare no conict of interest.

752

Impact of the sequence of modern combination

chemotherapy protocols on survival of patients with

advanced pancreatic cancer treated at the West German

Cancer Center Essen

Julius Röhrle1; Andreas Paul2,3; Peter Markus4; Brigitte Schumacher5; David

Albers5; Johanna Wendling1; Saskia Ting6; Bastian Mende7; Marlene

Massmann1; Isabel Virchow1; Vivian Rosery1; Katharina Laue1; Gregor

Zaun1,8; Karina Kostbade1; Michael Pogorzelski1; Sven-Thorsten Liers1,8;

Kurt Werner Schmid3,6; Hans-Ulrich Schildhaus3,6; Martin Schuler1,3; Stefan

Kasper-Virchow1,3; Jens Siveke1,3,8; Marcel Wiesweg1

1West German Cancer Center, Department of Medical Oncology, University

Hospital Essen, Essen, Deutschland

2West German Cancer Center, Department of General, Visceral and Transplant

Surgery, University Hospital Essen, Essen, Deutschland

3German Cancer Consortium (DKTK), Partner site University Hospital Essen,

Essen, Deutschland

4Elisabeth Hospital Essen, Department of General Surgery and Traumatology,

Essen, Deutschland

5Elisabeth Hospital Essen, Department of Gastroenterology, Essen, Deutschland

6West German Cancer Center, Institute of Pathology Essen, University Hospital

Essen, Essen, Deutschland

7Central Pharmacy, University Hospital Essen, Essen, Deutschland

8Bridge Institute of Experimental Tumor Therapy, West German Cancer Center,

University Hospital Essen, Essen, Deutschland

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the

most deadly cancers. In clinical studies modern combination therapy

protocols such as FOLFIRINOX or gemcitabine/nab-paclitaxel (G/nP)

demonstrated superior survival outcomes over monochemotherapies.

In clinical practice, many pts receive a sequence of both regimens as

rst- and second-line palliative treatment. However, there is no guidance

regarding a preferred order.

Methods: We retrospectively analyzed the clinical outcome of patients

with PDAC treated at the West German Cancer Center Essen, an

Oncology Center of Excellence designated by the Deutsche Krebshilfe,

from 2014 to 2020. Patient data and treatments were retrieved from the

hospital information system. Endpoints included overall survival (OS),

progression-free survival (PFS) and overall response rates (ORR) for all

treatment lines as well as disease-free survival (DFS) for curatively treated

patients.

Results: We identied 170 patients with available follow-up. Of those,

146 (85%) pts received palliative CTX for metastatic or locally advanced

PDAC. Median OS in this group was 8.2 months (95% CI 6.9-9.7). 24

patients (15%) underwent curatively intended surgical resection, of which

21 relapsed. Median DFS in resected patients was 14.1 (12.0-21.5) months,

and median OS 27.7 (21.4-NE) months. Median PFS upon rst palliative

chemotherapy was 4.1 (3.1-6.0) months. In patients who received at least

two lines of therapy, rst-line treatment with FOLFIRINOX did not trans-

late into superior OS as compared to alternative multiagent protocols

including G/nP (median OS 12.1 months [9.5-18.5] vs. 12.0 [9.7-16.9]).

Second-line regimens had similar PFS (overall log-rank p=0.85, median

PFS2 2.3 [1.8-2.9], per-regimen median between 1.8 and 3.9 months).

Prolonged survival times were observed in individual pts, which associ-

ated with unique genomic features enabling targeted treatment options.

Conclusions: e choice of rst-line chemotherapy, FOLFIRINOX or

G/nP, had no impact on survival outcomes of this real-world cohort of

PDAC patients.

Disclosure Statement: e authors declare no conict of interest.

792

Molecular characterization of biliary tract cancers treated at

the West German Cancer Center Essen

Timm Reißig1,2,3,4; Ilektra-Antonia Mavroeidi3; Melanie Guyot3,5;

Sven-Thorsten Liers1,2,4; Thomas Herold4,6; Stefan Kasper-Virchow3,4;

Martin Schuler3,4; Andreas Paul4,7; Hans-Ulrich Schildhaus4,6;

Jens Siveke1,2,3,4

1Bridge Institute of Experimental Tumor Therapy, West German Cancer Center,

University Hospital Essen, Essen, Deutschland

2Division of Solid Tumor Translational Oncology, German Cancer Research

Center (DKFZ), Heidelberg, Deutschland

3Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, Essen, Deutschland

4German Cancer Consortium (DKTK), Partner Site University Hospital Essen,

Essen, Deutschland

5Department of Gastroenterology, Oncology and Hematology, Diabetology and

Rheumatology, Marien-Hospital Wesel, Wesel, Deutschland

6Institute of Pathology, West German Cancer Center, University Hospital Essen,

Essen, Deutschland

7Department of General, Visceral and Transplantation Surgery, University

Hospital Essen, Essen, Deutschland

Background: Next to their anatomic presentation, biliary tract cancers

(BTC) are dened by distinct molecular features, which enable an increas-

ing number of targeted treatment options. We here describe the muta-

tional landscape of a BTC cohort with particular focus on DNA damage

repair (DDR) systems.

Methods: We retrospectively analyzed the clinical outcome and mutational

status of patients with BTC treated at the West German Cancer Center

Essen from 2016 to 2020. Patient data and treatments were retrieved from

the hospital information system. We performed two targeted DNA-based

assays (customized NGS panel and AmoyDx® HRD Focus Panel) and one

RNA-fusion assay (FusionPlex CTL Panel [Archer]). Survival and addi-

tional clinical endpoints were associated with the mutational status.

Results: We analyzed 55 patients including 35 intrahepatic cholangio-

carcinoma (iCCA, 64%), 12 perihilar CCA (pCCA, 22%), 5 distal CCA

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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts262

(dCCA, 9%) and 3 gallbladder cancers (GBC, 5%) with both DNA-based

assays. e most commonly mutated genes were TP53 (17/55, 31%),

KRAS (13/55, 24%), ARID1A, BAP1, IDH2 and PIK3CA (each 5/55, 9%).

Alterations in the DDR pathway genes were detected in 4 patients (4/55,

7.3%). Additionally, 14 samples were analyzed with the RNA-fusion assay.

We identied four FGFR2 fusions (with dierent fusion partners, 4/55,

7.3%) and one NRG1 fusion (1/55, 1.8%). Association with clinical data

will be reported at the meeting.

Conclusion: We report a well-characterized cohort of BTC patients ana-

lyzed with three molecular assays. e 7% of BTC patients with DDR

deciency might be another subgroup suitable for targeted therapies, i.e.

PARP inhibition.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

933

The impact of CD4+T cell plasticity in colorectal cancer on

immunotherapeutic strategies

Leonie Konczalla1,2; Filippo Cortesi1; Tabea Sturmheit3; Yogesh Kumar1;

Ramez Wahib1; Jenny Krause4; Anastasious Giannou1; Nathaniel Melling1;

Daniel Perez5; Jakob Izbicki1; Samuel Huber4; Nicola Gagliani1,4

1University Medical Center Hamburg-Eppendorf, Department of General,

Visceral and Thoracic Surgery, Hamburg, Deutschland

2niversity Medical Center Hamburg-Eppendorf, Mildred Scheel Cancer Career

Center , HaTriCS4, Hamburg, Deutschland

32cureX A/S, København, Dänemark

4University Medical Center Hamburg-Eppendorf, Centre for Internal Medicine, I.

Department of Medicine, Hamburg, Deutschland

5Asklepios Klinik Altona, Hamburg, Deutschland

Background: Immune cells play a pivotal role in the tumorigenesis as well

as in therapy. Despite extensive research, the role of Foxp3+TREGas well as

TH17 cells is still debated. However, with regard to combating cancer with

immunotherapies, the division in tumorpromoting and -inhibiting cells

is becoming increasingly important to pave the way for ecient therapy.

Methods: Human single-cell RNAseq was combined with cutting-edge

mouse models to dissect function and developmental trajectory of

IL-17A+Foxp3+CD4+T cells in CRC.

Result: In an unsupervised analysis of human and murine CD4+T cells,

we noticed a large proportion of IL-17A+CD4+T cells, also express-

ing the hallmark feature of TREG, forkhead box P3 (Foxp3). Our murine

data show strong tumor-fostering activity of IL17A+FoxP3+CD4+T cells.

Cellular trajectory was unveiled by RNAseq of human tumor-inl-

trating T-cells and T cell receptors. Interestingly, these data revealed

the ability of Foxp3+T

REG to perform a full conversion to TH17 and

IL-17A+Foxp3+CD4+T cells. However, classical TH17 cells were not able

to convert to IL-17A+Foxp3+CD4+T cells. Importantly, our data suggested

that trajectory is regulated by co-inhibitory receptor expression.

Discussion: In CRC IL-17A+Foxp3+CD4+T cells are present, which are

pro-tumorigenic while suppressing inammation. is stands in contrast

to the long-believed causality of inammation and tumor growth. One

reason for these discordant functions may be the dierent cellular pre-

cursors of IL-17A+Foxp3+CD4+T cells. eir abundance might be modu-

lated by co-inhibitory receptors. is might determine the ecacy of the

immune therapy as well as patient outcome.

Conclusion: e cellular origin of pro-tumorigenic IL-17A+Foxp3+CD4+T

cells is critical, as it could determine dierent therapeutic strategies to

contrast the cancer fostering activity. is may help to generate promising

immunotherapies for CRC patients.

Disclosure Statement: e authors declare no conict of interest.

972

Ecacy of Carboplatin and Cabazitaxel in Heavily Pretreated

Patients with Metastatic Castration-Resistant Prostate Cancer

Nadja Strewinsky1; Sergey A. Dyshlovoy1,2; Victor M. Schüttfort3;

Derya Tilki2,3; Su Jung Oh-Hohenhorst2,4; Markus Graefen3;

Carsten Bokemeyer1; Gunhild von Amsberg1,2

1University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum

– University Cancer Center Hamburg (UCCH), Department of Oncology,

Hematology and Bone Marrow Transplantation with Section Pneumology,

Hamburg, Deutschland

2University Medical Center Hamburg-Eppendorf, Martini-Klinik, Prostate Cancer

Center, Hamburg, Deutschland

3University Medical Center Hamburg-Eppendorf, Department of Urology,

Hamburg , Deutschland

4Centre de recherche du Centre hospitalier de l’Université de Montréal

(CRCHUM) et Institut du cancer de Montréal, Montréal, Kanada

Background: Increasing treatment pressure of mCRPC patients are likely

causative for the rising numbers of aggressive variants of prostate cancer

(AVPC) with visceral metastasis and neuroendocrine features. Compared

to CBZ monotherapy, cabazitaxel (CBZ) combined with carboplatin

(CARBO) has demonstrated improved ecacy in AVPC.

Methods: We retrospectively analysed mCRPC patients who received

CBZ plus CARBO therapy at the University Medical Center Hamburg-

Eppendorf between 12/2017-09/2020. Moreover, we investigated the in

vitro eects of CBZ+CARBO in human PCa cells exhibiting dierent lev-

els of resistance to taxanes as well as changes in cellular proteome.

Result: In total, 16 patients were eligible for analysis with a median age

of 63 years. At treatment initiation 75% had visceral metastases. On aver-

age, men had previously received 3.5 lines of treatment, including CBZ

monotherapy. A PSA decline ≥30% was seen in 44% of patients. Median

PFS was 4.5 months. Patients who completed all 6 cycles of CBZ+CARBO

achieved sustained disease stabilisation in 56% of cases. Despite prior

treatment with CBZ, 5 of the 11 pre-treated patients showed stable disease.

In vitro experiments revealed synergistic eects of CBZ+CARBO in

AR+ and AR- neuroendocrine PCa cells. Additive eects were detected

in AR- Du145 and PC3 cells, and in their docetaxel resistant (DR) sub-

lines. Remarkably, the latter showed increased sensitivity to CARBO.

Proteomics analyses of DR cells treated with either CBZ+CARBO or

CARBO alone revealed suppression of several drivers of epithelial-

mesenchymal transition and neuroendocrine dierentiation, such as

EGFR, STAT3 and Wnt/β-catenin signalling.

Discussion: Our patient’s data were in line with previous trials. Notably,

CBZ pre-treated patients responded to CBZ+CARBO and the in vitro data

suggest partial inversion of the AVPC phenotype.

Conclusion: Our data conrm ecacy of CBZ+CARBO combinational

therapy in AVPC. e synergistic eects as well as in increased sensitivity

to CARBO in DR cells may be related to a partial inversion of the AVPC

phenotype.

Disclosure Statement: e authors declare that there are conicts of interest. e

connections were submitted to the congress organizer KUKM GmbH and KUKM

can disclose them if needed.

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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 263

1026

Establishment of a living biobank of Pancreatic

Adenocarcinoma organoids to develop personalized

approaches

Christopher Neumann1; Marie Bossen1; Sandra Liebs2,3; Jana Ihlow4;

Georg Hilfenhaus1; Marcus Bahra5; Loredana Vecchione1;

Johann Pratschke6; Sebastian Stintzing1; Ulrich Keilholz2; Uwe Pelzer1

1Department of Internal Medicine, Division of Hematology, Oncology and

Tumorimmunology, Charité Campus Mitte, Charité - Universitätsmedizin Berlin,

Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin,

and Berlin Institute of Health, Berlin, Deutschland

2Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,

corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin,

and Berlin Institute of Health, Berlin, Deutschland

3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

4Institute of Pathology, Charité Campus Mitte, Charité - Universitätsmedizin

Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu

Berlin, and Berlin Institute of Health, Berlin, Deutschland

5Center for oncological upper abdominal surgery and robotics, Hospital

Waldfriede, Berlin, Deutschland

6Department of Surgery, Charité Campus Mitte & Campus Virchow Klinikum,

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität

Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin,

Deutschland

Introduction: Pancreatic adenocarcinoma is one of the most lethal types of

cancer and is progressively gaining attention since it is predicted to be the

second most common lethal cause of cancer by 2030. Recent approaches

have been made to explore the potential of patient-derived organoid

pharmacotyping as a possibility towards precision medicine. us, rst

correlations between the clinical response to therapy in patient-derived

organoids and PDX-models were made. is is a feasibility study of build-

ing up a biobank from various sample types of pancreatic cancer.

Methods: Resection samples and biopsies were minced, digested and l-

tered. Malignant cells of ascites were separated from lymphocytes through

magnetic labelling. Cells were than transferred into Matrigel and grown

in human complete feeding medium, including R-Spondin and WNT3a-

conditioned medium, 100 ng/ml Noggin, 100 ng/ml hFGF10 and 50 ng/

ml hEGF. e project is supported by the Charité Clinical Scientist pro-

gram and the “Berliner Krebsgesellscha e.v.”.

Results: Between Oct 2021 and Mar 2022 a total of 10 organoid cultures

were established from 26 pts, including tissue from surgical resections of

the primary tumor (5/10), biopsies of liver metastases (4/10) and ascites

(1/10). e total isolation rate was 69% (18/26) with an overall establish-

ment rate (min. 3 passages) of 38% (10/26).Histopathological characteris-

tics (HE-, Ki67-, TP53-staining) of the organoids proved to be consistent

with the tumor samples reecting high consistencies.

Conclusion: is work focused on the feasibility of building up a bio-

bank of pancreatic cancer organoids from various dierent sample types,

including resection samples, biopsies and ascites. In nearly 40% of the

samples, organoids were successfully established and used for further

functional analysis. e primary aim of this biobank being the exploration

of primary and secondary resistance pathways. Organoids will be exposed

to sequential cycles of chemotherapy (mFOLFIRINOX vs. Gemcitabin/

Paclitaxel) and resistance mechanisms will be identied on a proteomic

level.

Disclosure Statement: e authors declare no conict of interest.

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Autorenindex

A. Kestler, H. 131

Abbosh, C. 218

Abdullayev, N. 787

Abenhardt, W. 252

Abou Kors, T. 131

Abou-Madian, Ahmed Y. 522

Abramova, A. 740

Abramson, J. 968, 967

Ackermann, L. 808

Ackermann, U. 359

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Adamietz, Irenäus A. 783

Adams, Hans-Peter 902

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Adeboyeje, G. 1003, 1005

Adler, A. 855

Aehnelt, M. 642

Aolter, A. 143, 576

Aftimos, P. 504

Agaimy, A. 761

Agarwal, A. 208

Aguado Barrera, M. E 946

Aguilar, L. 758

Aguilar-Cordova, E. 758

Ahmad, Azura R. 840, 165

Ahrens, K. 898

Ahrens, M. 158

Aigner, C. 518

Akbaba, S. 360

Aker, S. 675

Akopov, A. 33

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Aktas, B. 190

Al Ahmar, E. 430

Alakus, H. 810

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Aldisi, R. 379

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Algül, H. 297, 950

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Alonso Gordoa, T. 308

Alt, J. 370

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Ameline, B. 628

Amin, A. 534

Amin, S. 1005, 1003

Ammer, Laura-M. 613

Ammerpohl, O. 131

Anand, S. 210

Anders, C. 608

Anderson Jr, Larry D. 150, 709, 560

André, F. 608

André, T. 990

Andreou, D. 804

Andrulat, A. 114

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Angeles, Arlou K. 482

Angelescu, K. 1032

Anjum, R. 989

Ankerst, D. 92

Ansmann, L. 161, 614, 706

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Arsov, C. 852

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Audigier-Valette, C. 920

Augustin, M. 128

Autengruber, A. 266

Avery, E. 414

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Backsch, C. 662

Badros, Ashraf Z. 534

Bady, E. 1029, 1054, 1031, 1053

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Bahra, M. 1026

Bai, Y. 748

Baier, D. 1045

Balasubramanian, G. 829

Bald, T. 551

Baldus, C. 638, 679

Balermpas, P. 476

Balic, M. 66, 504

Balk, M. 261

Ballweg, A. 419

Balsen, Eva-M. 1023

Baltas, D. 513, 591

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Balzer, B. 390

Balzer, S. 659, 987

Bamberger, N. 398

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Banito, A. 749

Bankfalvi, A. 199

Bannert, H. 233

Banys-Paluchowski, M. 269, 676

Bar, J. 256

Baran, C. 458

Baranowsky, A. 120

Bardia, A. 936, 283

Barenboim, M. 628

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Barker, Scott S. 255

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Barrett, J. Carl 911, 218

Barrios, C. 283

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Bartenstein, P. 613

Barthelemy, P. 222, 158

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Bartsch, R. 66

Bartzke, C. 638

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 265

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Bast, C. 588

Basteck, S. 765

Basu, O. 673

Batenhorst, I. 297

Bauer, E. 502

Bauer, L. 522

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Bauer, S. 486

Bauer, T. 518

Bauerfeind, I. 114

Bauernfeind, Franz-G. 551

Bauersachs, R. 621

Bauerschmitz, G. 353

Baues, C. 339

Baumann, F. 321, 562, 773,

778, 20, 548, 570,

631, 647, 673, 727,

735, 767, 772

Baumann, K. 674

Baumann, M. 415

Baumann, S. 975

Baumgarten, P. 568

Baumhoer, D. 628

Baust, K. 934

Bayerlova, M. 815

Bazhin, A. 219

Beach, CL 287

Becher, B. 307

Beck, Eva M. 1024

Becker, G. 847

Becker, I. 476

Becker, Jan C 573

Becker, M. 209, 243

Becker, M. 914

Becker, N. 852

Becker, S. 299

Becker, S. 565, 580

Beckert, H. 518, 622, 416

Beckhove, P. 613

Beckinger, S. 490, 179

Beckmann, H. 905

Beckmann, M. 31

Bedke, J. 153, 158, 266

Bednarsch, J. 174

Beer, K. 662, 680

Beerenwinkel, N. 745

Behlendorf, T. 474, 869

Behr, Bj. 251

Behrens, B. 745

Behrens, F. 909

Behringer, J. 245

Behzad, A. 720, 951

Beier, D. 779

Beier, F. 739

Beißbarth, T. 1, 808, 815, 583

Beitzen-Heineke, A. 731

Beksac, M. 150

Belanov, S. 325

Belka, C. 359

Belleli, R. 33

Beller, R. 2, 1060

Bellet, M. 283

Belleville, E. 385

Belotte, J. 636

Beltzig, L. 43, 52, 53, 768

Belyaev, O. 788

Belz, H. 266

Ben Khaled, N. 425

Benary, M. 260

Benckendor, J. 131

Bende, K. 556

Bendrich, S. 34, 101, 227, 757

Bengsch, F. 211

Benitez, D. 523, 788

Benndorf, M. 591

Benner, A. 852

Bennett, E. 33

Bennouna, J. 942

Bennstein, Sabrina B. 1060

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Benz, Stefan R. 1039

Benz-Rüd, I. 128

Bercker, S. 1023

Berdeja, J. 560, 709

Berg, J. 156

Berg, T. 211

Bergelt, C. 871, 976

Berger, K. 621, 779

Berger, Martin R. 368

Berger, W. 1045

Bergholz, A. 876

Bergmann, L. 152, 153, 158

Bergmann, M. 456

Beringer, A. 223

Berking, C. 456

Berlit, S. 522

Bernabe, R. 868

Berndt, U. 198

Berner, F. 551

Bernhardt, C. 135, 245

Bernhardt, K. 300

Berton, D. 990

Bertram, H. 532

Bertram, M. 519

Besse, B. 255

Best, J. 425

Bestvater, F. 749

Bethmann, D. 751

Bettinger, D. 425

Beutel, G. 1014

Beutel, Manfred E. 996, 997, 1057

Beutner, D. 63

Beyer, S. 118, 132, 571

Bhadri, V. 450

Bieback, K. 143

Bieber, B. 646, 513

Bielack, S. 628

Bierbaum, V. 515, 531

Bigot, P. 222

Bilsing, B. 615

Binninger, A. 259

Birkenfeld, F. 739

Birkl-Toeglhofer, Anna M. 404

Birkner, T. 799, 1039

Biro, D. 555

Bischof, G. 975, 1022

Bischo, C. 136, 974

Bischo, H. 868, 908, 413, 707

Bitter, E. 912

Bittner, Ann-K. 157

Bitzer, M. 335

Bjelic-Radisic, V. 1027

Blais, Edik M 1005, 1003

Blakely, C. 50

Blankart, K. 278

Blankenstein, T. 681

Blanksma, A. 706

Blasi, M. 413

Blau, W. 410

Blay, Jean-Y. 906, 916

Bleckmann, A. 345, 391, 808, 815

Bleich, C. 137

Bleif, M. 847

Blessin, Niclas C. 1029, 1031, 1053, 1054

Bleumer, T. 1049, 1052

Bloch, W. 136, 575, 659, 974, 987

Bloedt, S. 914

Blohmer, Jens-U. 269, 504, 1027, 676

Blome, C. 905

Blum, Steven I. 920

Bobbili, D. 379

Bobeth, C. 531

Bochtler, T. 223

Bockmühl, U. 63

Boddu, V. 603, 1042

Bode-Greuel, K. 204

Bögemann, M. 67, 82, 158, 253,

266, 326, 898

Böger, D. 430

Bohle, R. 556

Böhmerle, W. 159, 1049, 1052

Bojarski, C. 855

Bokemeyer, C. 972, 976, 137, 312,

731, 895, 616

Bokemeyer, F. 137

Boklage, S. 1050

Bolenz, C. 79

Boleti, E. 158

Bollschweiler, E. 767

Bolm, L. 1009

Boltenhagen, Ursula. 692, 720, 951, 1067

Bölükbas, S. 433, 606

Bonci, Eduard-A. 269

Bondarenko, I. 908, 1036, 33

Bondarets, V. 929

Boni, V. 730, 990, 1055

Böning, G. 943

Boos, J. 673

Boppudi, Sanga M. 181

Borchardt, J. 306

Borchert, S. 622, 199, 416, 518

Borchmann, P. 339, 610

Borde, J. 361

Borges, V. 309

Borghaei, H. 920

Borghesi, G. 327

Borgmann, S. 1014

Borgovan, T. 989

Bornhäuser, M. 134, 804, 874

Bosancu, I. 40

Bösch, F. 219

Bösche, J. 90

Bossart, M. 341

Bossen, M. 1026

Bossert, J. 547, 1067

Boston, S. 608

Boström, Jan P. 783

Boström, K. 634

Bothur, S. 724

Bougatf, N. 191

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index266

Bourgeois, M. 739

Boz, S. 159

Bozorgmehr, F. 47, 244, 482, 500, 707

Bozzetti, T. 405

Bradley, William H. 674

Brähler, E. 996, 997

Brahmer, Julie R. 920

Braicu, Elena I. 291, 302

Branchi, F. 855

Brand, H. 722, 976

Brand, T. 278

Brandl, A. 524

Brandstetter Vilar, J. 768

Brandts, C. 510

Brauer, N. 625

Braulke, F. 866, 1006

Braumann, C. 814

Braun, M. 306, 114

Braun, R. 1009

Braun, T. 954

Brauner, R. 881

Braverman, J. 968

Bray, V. 256

Brcic, L. 416, 622

Breckner, A. 204

Breidenbach, C. 127

Breitenstein, U. 66

Brenner, H. 532, 358

Brenner, W. 756

Breuing, J. 914

Breyer, J. 79

Brichard, B. 450

Briers, E. 970, 946

Broadhurst, H. 911

Brockmeyer, P. 329

Broge, B. 204

Bronsert, P. 1009

Brors, B. 829

Brossart, P. 995, 551, 921, 262

Brown, Jennifer R. 349, 374, 411

Brown, J. 730, 1055

Bruch, D. 167

Brück, V. 522

Brückl, N. 94

Brückl, W. 40, 94, 280, 391, 777

Brufsky, A. 936

Brümmendorf, Tim H. 739

Bruners, P. 119

Brüning, F. 128

Brunner, C. 131

Brunner, J. 708

Brunner, M. 761

Brunner, T. 59, 74, 476, 714, 784,

786, 787, 789

Bruns, C. 502, 649, 810, 428

Bruns, R. 370, 840

Bryn, G. 239

Brzezicha, B. 524, 681

Brzoska, P. 835, 1068

Buchele, C. 578

Büchele, T. 504, 1027

Buchhold, B. 46

Buchholz, M. 814

Buchholz, T. 21, 22

Buchkremer, J. 855

Büchler, C. 347

Buchmann, J. 751

Büchner-Steudel, P. 198

Buckstein, R. 281, 282

Budach, V. 410, 884

Budach, W. 476

Buettner, F. 620

Buettner, R. 817

Bühler, H. 783

Bühn, S. 914

Bultjinck, R. 946

Büntemeyer, Tjark-O. 493

Büntzel, J. 430, 453, 686, 63

Büntzel, J. 465, 467, 682

Büntzel, Sören K. 682

Burdach, S. 628

Burderath, P. 199

Burger, M. 79

Bürger, T. 566

Burges, Alexander. 118, 132, 571

Burgués, Juan Miguel B. 891

Burke, John M. 891

Bürkel, F. 512

Bürkle, D. 103

Burn, Timothy C. 335

Burock, Susen 605

Bürrig, Karl-F. 751

Bürtin, F. 535

Busch, Chia-J. 63

Busch, H. 1042

Busch, U. 74

Büsch, C. 1065

Bushong, J. 920

Busse, A. 681

Büttner, R. 446, 510, 810, 912

Büttner, T. 79

Buziba, N. 716

Byers, L. 911

Byl, A. 398

Byrd, John C. 411

Byrne, J. 991

Bytyqi, F. 275

Cabanillas, M. 277

Cabuk, C. 40

Çakmak-Görür, N. 681

Calaminus, G. 934

Callenoni, M. 309

Calvert, Paula M. 674

Cameron, S. 293

Campbell, P. 414

Campbell, T. 560, 208, 709

Campillo, M. 669

Cannell, P. 956

Carbone, David P. 942

Cardoso, F. 870

Carey, L. 936

Carl, Ernst-G. 914

Carles, J. 327

Carmelo, V. 877

Carmen, L. 267

Caro, Reyes B. 920

Carr, P. 358

Carver, J. 989

Casper, J. 82

Castellano, D. 158

Castillo-Binder, P. 381

Cavailles, V. 828

Cavo, M. 560, 709, 208

Cedzich, C. 275

Chaft, J. 50

Chalabi, N. 223

Chalas, S. 655

Chalopin, C. 689

Chamorro-Vina, C. 1060

Chan, A. 553

Chan, Wai Y. 956

Chanan-Khan, A. 411

Chang, Ching-W. 283

Chang-Claude, J. 970, 358, 946

Chao, Y. 1064

Charalambous, N. 593

Chauchet, A. 891

Cheah, Chan Y. 516, 349

Chekerov, R. 302

Chella, A. 33

Chemnitz, J. 486

Chen, J. 1036

Chen, M. 534

Chen, Njin-Z. 119

Chen, Y. 908

Chen, Y. 817

Cheng, S. 956

Cheng, Y. 840, 942

Cheung, Matthew C. 891

Chiabudini, M. 135, 246

Chiocca, E. Antonio 758

Cho, Byoung C. 16

Chodan, W. 642

Chouaid, C. 868, 256

Choudhury, A. 970, 946

Choueiri, Toni K 151

Christmann, J. 788

Christmann, M. 43, 768

Christoph, B. 515

Christoph, Daniel C. 128, 416, 135,

256, 433, 606

Christopoulos, P. 47, 135, 244, 482,

500, 707, 413

Chugh, P. 911, 908

Chung, I. 413

Cicchetti, A. 946

Cidre-Aranaz, F. 749

Ciruelos, E. 210

Ciuleanu, Tudor-E. 920, 942

Claßen, Annika Y. 1041

Claus, R. 669

Clausen, S. 522

Clement, Joachim H. 323

Clements, A. 636

Clezardin, P. 120

Co, M. 956

Cobo-Dols, M. 942

Coelho, R. 640

Cofre, A. 453

Cohen, Johnathon B. 516

Coleman, Robert L. 1050

Collaud, S. 450

Combs, Stephanie E. 359

Concalves, A. 504

Conev, Nikolay V 908

Conrad, T. 209, 243, 404

Conradi, Lena-. 1, 292, 808, 815, 583

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 267

Conrads, K. 583

Cook, G. 534

Cook, N. 223

Coombs, Catherine C. 349, 516

Cords, H. 312, 418

Corradini, S. 118, 571

Corre, R. 989

Cortes, J. 936

Cortesi, F. 933

Cosenza, M. 586

Coto-Llerena, M. 104, 89

Coudert, B. 553

Coupland, S. 853

Cove-Smith, L. 868

Coym, A. 312

Cramer, T. 627

Crawford, D. 952

Creutzig, U. 673

Crispin, A. 947, 955, 1016

Croner, R. S. 604, 736, 742, 759, 781, 809

Crotta, A. 968, 967

Croydon, E. 1064

Crysandt, M. 486

Cubillo Gracián, A. 714

Cui, K. 950

Culmsee, C. 754

Cumin, C. 620

Cyprova, S. 450

Czauderna, C. 443

Czogalla, B. 132, 571

D’Angelo, Sandra P. 690, 700

Dacic, S. 50

Dadras, M. 251

Däggelmann, J. 136, 575, 659, 974, 987

Dahl, E. 174

Dahlmann, M. 404, 524, 605

Daley, W. 1036

Dalferth, R. 169, 172

Daltrozzo, T. 297

Dalvi, T. 908

Dambacher, S. 252

Damber, Jan-E. 328

Daniel, M. 572

Dannecker, C. 828

Darr, C. 82, 152

Darsow, M. 429

Darwich, A. 12

Das, P. 971

Däster, S. 89

Daunke, T. 490, 179

David, F. 379

Davids, Matthew S. 349

Davies, Faith E. 691

Dayan, D. 656, 658

D‘Cruz, C. 608

de Boer, C. 866, 1071, 1075

de Boniface, J. 269

De Braud, Filippo G. 255

De Geest, S. 180

de la Mora Jimenez, E. 942

De la Serna, J. 414

De Lazzari, N. 20, 562

de Oliveira, T. 808

De Oliveira, T. 583

De Ruysscher, D. 946, 970

de Schultz, M. 874

De Toni, E. 425

de Wit, M. 171, 945

DeArbeloa, P. 1005, 1003

Debatin, Nicolaus F. 1029, 1054

Debus, D. 73, 544

Debus, Jürgen P. 36, 47, 191, 234, 244,

360, 500, 578, 851, 852

Deckbar, D. 158

Decker, T. 246, 340

Degenhardt, T. 298

Degenkolbe, E. 898

DeGregorio, A. 1059

Deichmann, S. 1009

Deis, N. 888

Delebinski, L. 1015

Delforge, M. 709

Delker, A. 943

Delmastro, N. 171

Delmonte, A. 868

Demmler, R. 864

Denkert, C. 504, 1027, 114

Depenbusch, J. 197

Derani, H. 880

Dernoscheg, Marie-T.e 544

Deryal, M. 302

Desai, J. 690, 700

Dey, A. 218

Dhanasiri, S. 691

Dhar, A. 989

Di Bartolomeo, M. 1064

Di Micco, A. 534

di Micco, R. 269

Di Pace, B. 989

Di Pietro, A. 151

Diekmann, A. 161

Dielmann, A. 260, 563

Dienstmann, R. 906, 916

Dieras, V. 936, 283

Dierkes, S. 754

Diers, J. 396

Diestelhorst, A. 499

Dietlein, M. 339, 446

Dietrich, D. 663

Dietrich, S. 891

Dietz, A. 262, 63

Dietz, T. 844

Dietzel, F. 745

Diez-Campelo, M. 281, 282

Dimopoulos, M. 150, 971

DiNardo, C. 956

Dinges, S. 522

Dinkel, A. 297, 92, 359

Dintner, S. 669

Dippmann, C. 445, 680

Dirksen, U. 450, 647, 673, 749, 765

Disler, M. 640

Distel, L. 607, 512

Distelrath, A. 66

Dittmar, G. 605

Dobler, F. 828

Doege, D. 532

Doehn, C. 780, 794, 795, 898

Doescher, J. 131

Döhner, H. 287

Dolan, S. 414

Doleschall, Anna D. 1041

Dommerich, S. 262

Donath, S. 34, 78, 101, 227, 747, 757,

776, 584

Donaubauer, Anna-J. 476

Doppler, A. 456

Dörenberg, J. 174

Dörfel, S. 280, 245, 259, 869

Döring, K. 713, 776

Döring, S. 673

Dornstauder, E. 881

Dörr-Harim, C. 165

Dørumn, A. 674

Dostalek, L. 269

Doyle, C. 309

Dräger, Desiree L. 21, 22, 23

Drageset Haakensen, V. 256

Dreimann, M. 895

Dreismann, L. 26

Dressler, J. 146

Dreyling, M. 516

Drilon, Alexander E. 255, 277

Dröge, Leif H. 34, 78, 101, 227,

713, 747, 757,

776, 1077, 584

Dröge, P. 515, 531, 934

Droste, A. 451, 473, 471

Drzezga, A. 446

Duan, T. 730

Dubecz, A. 40

Ducreux, M. 32

Dudas, C. 485

Dueñas, N. 379

Dum, D. 1053

Dummer, R. 73

Duran Cortes, M. 171

Duran-Pacheco, G. 223

Dürsch, H. 1067

Dürst, M. 445, 662, 680

Dusel, J. 1018

Duska, L. 730

Dutailly, P. 222

Duyster, J. 307, 1042

Dwinger, S. 731

Dysarz, J. 302

Dyshlovoy, Sergey A. 972

Dytfeld, D. 971

(OSHO), East German Study

Group of Hematology

and Oncology 228, 229

Ebeling, M. 959

Eberhardt, Ina M. 529

Eberhardt, Wilfried Ernst E. 280, 135

Eberl, I. 49

Eberle, A. 532

Eberle, M. 669

Ebert, M. 1039

Eccles, L. 920

Eckert, K. 673

Eckford, R. 415

Eckstein, M. 79, 261, 458, 476

Edelmann, F. 159

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index268

Edelmann, M. 808, 583

Egerer, G. 486

Egger, E. 302

Eggers, E. 245

Eggert, A. 201

Egyed, M. 166

Ehlert, S. 198

Ehmann, M. 522

Ehneß, R. 898

Ehrenthal, J. 360

Ehret, F. 847, 884

Ehrmann, J. 648

Eich, Hans T. 268, 573, 450

Eichbaum, M. 302

Eichenauer, D. 339

Eichenauer, Rolf H. 780, 794, 795

Eichhorn, A. 721, 506

Eichhorn, F. 482, 707

Eichhorn, Martin E. 413

Eichhorst, B. 374

Eichkorn, T. 36, 47, 244, 500, 578, 851

Eichler, MSc., M. 804, 702

Eickho, R. 85

Eidt, S. 94

Eifert, T. 323

Eigentler, T. 267

Einsele, H. 560, 709

Einspieler, I. 813

Eisert, A. 912

Ek, T. 450

Ekanem, Ima-O. 823

El Shae, R. 78, 101, 191, 227,

244, 360, 500,

747, 757, 47

Eliason, L. 991

Ellard, Susan L. 990

Ellenrieder, V. 293

Ellinger, J. 79, 551

Elmers, S. 826

El-Rajab, I. 617, 741

Elshiaty, M. 482

Elter, T. 980

Emmler, A. 352

Emons, G. 594

Endres, M. 159

Engel, C. 361

Engel, E. 246

Engel, J. 311, 441, 539, 114

Engeland, K. 381

Engels, N. 1

Engert, A. 339

Englmeier, F. 391

Erb, C. 238

Erben, P. 79

Erber, R. 31

Erbersdobler, A. 880

Erbes, T. 586

Ercan, C. 89, 104

Ercan, H. 562

Erdem, M. 627

Erdmann, G. 325

Erickson, N. 298

Ernst, C. 361

Ernst, J. 292

Ernst, J. 5, 857

Ernst, K. 737

Ernst, M. 996, 997

Ernst, P, 323

Ernst, T, 100, 430, 961, 1056

Ernstmann, N, 161

Erschig, R. 673

Eschbach, J. 810

Eschmann, S. 1066

Escriu, C. 50

Escudier, B. 158

Esposito, I. 745

Esser, K. 405

Esser, P. 5, 610, 616

Eto, M. 308

Ettl, T. 111

Ettrich, Thomas J. 425

Evans, B. 1044

Everest-Dass, A. 620

Evers, G. 345

Evert, K. 111

Evripidou, G. 788

Exner, S. 684

Exner, S. 909

Eyl, Ruth E. 358

Eymard, Jean-C. 222

Eyre, Toby A. 349, 516

Ezić, J. 131

F.E. Barth, T. 131

Faber, J. 997

Fabre, S. 281, 282

Faehling, M. 1066

Fähndrich, S. 204

Failing, T. 78

Faitg, T. 690, 700

Faivre-Finn, C. 868

Fakhri, B. 349, 516

Falk, M. 554

Falkenthal, J. 624

Fallscheer, S. 1066

Faltus, T. 198

Fan, S. 583

Fang, N. 817

Farcy-Jacquet, Marie-P. 970

Farwick, N. 31

Fasching, Peter A. 31, 504, 1027, 676

Faulhaber, Eva-M. 512

Faust, E. 181

Fear, S. 916

Feder, I. 523, 788

Fedier, A. 640

Feeney, K. 942

Fehlauer, F. 909

Fehm, T. 340, 380, 405, 590,

740, 745, 748, 785,

954, 1059, 676

Feil, C. 368

Felberbaum, R. 656, 658

Feldmann, G. 995, 921

Feliciano, Joana G 877

Felip, E 33, 370, 989

Felser, S 228, 229

Fenaux, P. 281, 282

Feng, W. 309

Fennell, Jamina T. 513

Fenske, T. 516

Ferrajoli, A. 374

Ferrant, E. 166

Ferraro, F. 931

Ferreira, Cesaltina L. 716

Fetzner, Ulrich K. 767

Feuchter, J. 716

Feuchtinger, T. 356

Feufel, M. 397, 889

Feyerabend, S. 328, 327

Fichte, S. 847

Ficker, J. 94, 777

Fiebig, C. 233

Fiedler, R. 472

Field, J.K. 256

Fiesel, P. 829

Fietkau, R. 254, 261, 476, 512, 256

Filippi, A.R. 256

Filipski, K. 567

Finas, D. 1004

Fink, A. 954, 1059

Finke, G. 1030

Finke, I. 675

Finkelmeier, F. 425, 443

Finn, Richard S. 32

Finster, Agnes M.E. 829

Fisch, D. 707

Fischer, J. 78

Fischer, Laura A. 34, 101, 227,

747, 757, 776

Fischer, R. 912

Fisseler-Eckho, A. 181

Fitilidis, K. 462

Fizazi, K. 326, 327, 328, 952

Flach, M. 555

Flachs-Nóbrega, S. 529

Flatz, L. 551

Fleckenstein, K. 522

Fleischmann, B. 869

Fleitz, A. 135, 280, 391

Fleming, Evelyn. L. 636

Fleuter, C. 605

Flier, A. 99

Flinn, I. 516

Flock, F. 656, 658

Flörcken, A. 82, 152, 158

Fluck, M. 73

Flügen, G. 744

Fogliatto, Laura M. 166

Fokas, E. 1039

Folchini, Decio M. 233

Foller, S. 100

Follmann, M. 914

Follows, G. 166

Fong Ng, T. 956

Forget, F. 674

Foroutanpour, K. 868

Forrester, T. 436

Forschner, A. 73

Forstbauer, H. 103

Forster, A. 368

Förster, S. 1039

Forstner, A. 379

Fragoulis, A. 627

Frank, T. 297, 359

Franke, Fabio A. 1074

Franke, K. 612

Franke, s. 59

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 269

Franken, A. 745, 590, 380, 740

Freiberg-Richter, J. 211

Freidank, A. 754

Freitag, D. 568

French, P. 277

Frenkl, T. 337

Frenz, S. 914

Frerichs, W. 312, 418, 871

Freudlsperger, C. 360

Frey, B. 476

Freyer, B. 905

Freyer-Adam, J. 46, 975, 1022

Friedberg, JonathanW. 891

Friederich, Hans-C. 324, 360

Friedl, Thomas W. P. 340, 954, 1059,

676, 380

Friedman, E. 361

Friedrich, M. 616, 699, 1030

Friedrich, S. 1061

Fries, J. 661, 701, 698

Fritsch, R. 103

Fröhlich, K. 586

Fröhlich, S. 269

Frohwitter, G. 458

Frontado Grae, Freddy J. 995

Fruehauf, S. 245

Fruendt, T. 425

Fuchs, M. 339

Fuentes Pradera, J. 674

Fuhr, R. 494

Funk, C. 749

Funke-Lorenz, C. 307

Furlanetto, J. 504

Furman, Richard R. 411

Fürweger, C. 884, 847

Gaedcke, J. 1

Gagliani, N. 933

Gainey, M. 591

Gaipl, U. 476

Gaisa, N. 174

Gaisser, A. 415

Gaissmaier, L. 482

Gajate, P. 222

Gajda, Mieczyslaw R. 662

Galle, Peter R. 32, 211

Gallwas, J. 353, 588

Galonska, L. 574

Galuba, J. 606

Gambara, G. 524

Ganguli, A. 881

Ganly, Peter S. 374

Garassino, Marina C. 370, 868, 908, 256

García, Marc D. 1064

Garcia-Manero, G. 281, 282

García-Márquez, M. 502, 649, 428

Garcia-Saenz, Jose A. 436

Garlipp, B. 736, 738

Garon, Edward B 16

Garrido, F. 828

Garrido, P. 256

Garside, J. 1050

Gärtner, B. 975

Gasche, N. 1037

Gaser, D. 356

Gasimli, K. 565, 580

Gasiorowski, R. 956

Gasparri, Maria L. 269

Gasparro, D. 328

Gaß, P. 31

Gaßler, N. 662

Gaßmann, Karl-G. 233

Gastinger, I. 736, 738, 742

Gathof, B. 502

Gauler, T. 262, 63

Gauß, G. 2, 673, 1060

Gautschi, O. 255

Gawish, A. 784, 786, 789, 74

Gay, C. 911

Geater, Sarayut L. 16

Gehlhaar, A. 167

Geisen, S. 53

Geissler, J. 906, 916

Gelderblom, H. 450

Gemoll, T. 1042

Gengenbacher, L. 73

Gentilini, O. 269

George, Julie 502

Geppert, Carol I 864

Gerber, J. 302

Gerger, A. 103

Gerken, M. 355, 441, 462, 903,

492, 452, 515, 531

Gerlach, R. 621

Germer, Christoph-T. 396

Germing, U. 281, 282

Gerson, James N. 516, 349

Gerthofer, V. 611

Geue, K. 699

Geyer, S. 102

Ghadimi, M. 1, 292, 593, 594,

808, 583, 529

Ghadjar, P. 591

Ghamande, S. 730

Ghasemi, D. 737

Ghatage, P. 730

Ghataorhe, P. 991

Ghia, P. 166, 349, 411, 414, 516

Gianni, L. 936

Giannou, A. 933

Gierke, B. 590

Giese, N. 1002

Gieseler, F. 603, 1042

Giesemann, N. 874

Giesen, N. 1041

Giesler, S. 307

Giessen-Jung, C. 1014

Giladi, M. 460

Gilbert, L. 730, 990, 1055

Gildehaus, Franz-J. 943

Gillespie-Twardy, A. 374

Giordano, Frank A. 921

Girard, N. 256

Gires, O. 1042

Gitlitz, B. 33

Gkika, E. 714

Glade, J. 413

Glajzer, J. 458, 493

Glas, M. 254

Glaser, M. 454

Glaser, M. 912

Glaspy, J. 1036

Glaß, B. 968, 967

Glien, A. 474

Glowik, R. 291

Glowka, T. 995

Gnahatin, F. 823

Gockel, I. 399, 643, 689, 697

Goebel, Anna-M. 673

Goebell, Peter J. 67, 128, 153, 898

Goedicke-Fritz, S. 426

Goeppner, D. 73

Goerling, U. 857

Goertz, S. 625

Goetz, C. 739

Goetze, Thorsten O. 85, 357

Gökkurt, E. 357

Golan, T. 950

Gold, J. 726

Goldbrunner, R. 254

Goldhardt, T. 808, 583

Golding, S. 223

Goldman, Jonathan W 908

Goldschmidt, H. 630, 709, 208

Golla, A. 499

Göllner, S. 403

Gonçalves, M. 86

Gonzalez-Carmona, Maria A. 425, 921, 995

González-Martín, A. 654, 674

Göppner, D. 267

Gorantla, H. 603

Gorantla, Sivahari P. 1042

Görner, M. 262

Gostian, Antoniu-.261, 432, 476

Goto, K. 255

Götte, M. 2, 20, 617, 625, 647,

673, 741, 765, 1060, 356

Götz, M. 276

Götze, L. 200

Götze, T. 989

Grabbert, M. 327

Grabellus, F. 433

Grabher, P. 984

Grabowski, J. 654, 674, 636

Grabowski, M. 809

Grade, M. 1

Graefen, M. 972, 1031

Graf, K. 753

Graf, M. 441

Graf, S. 233

Grah, C. 135, 964

Grammatikopoulou, T. 866, 1075,

1075, 1073

Grapp, M. 324

Gratzke, C. 327, 591, 881, 359

Gravis, G. 158

Gravis-Mescam, G. 151

Gray, Heidi. J. 636

Grecea, D. 436

Gren, K. 655

Grehn, C. 40

Greif, P. 537, 555

Greil, R. 339, 891, 103

Greimelmaier, K. 622

Greiner, V. 134

Greiner, W. 961, 1056

Greiß, F. 159, 791

Greve, J. 131

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index270

Greve, M. 594

Gridelli, C. 989

Griesel, M. 716

Griesinger, F. 50, 135, 280, 370,

391, 694, 706, 712

Griewatz, J. 720

Grith, A. 758

Grillenberger, A. 783

Grimm, Marc-O. 128, 151, 158, 266

Grimmelmann, I. 267

Grimmig, T. 385

Gröger, C. 146

Groh, S. 22, 21

Grohé, C. 1007

Gröhnke, S. 826

Gröschel, A. 135

Grosicki, S. 971

Groß, J. 299, 102

Große Lackmann, K. 721, 506

Große-Thie, C. 228, 229

Gross-Goupil, M. 158

Großkinsky, U. 296

Groß-Langenho, M. 881

Groß-Opho-M., C. 980

Grosu, Anca-L. 140, 454, 460, 513,

591, 646, 714

Grote, L. 150

Groth, A. 135, 280

Groth, J. 410

Grove, C. 956

Grüllich, C. 67

Grün, J. 229

Gründker, C. 353, 588

Grundmann, H. 405

Grundmann, N. 618

Grundtner, P. 261

Grunert, C. 681

Grunert, M. 959

Grünewald, Thomas G.P. 749

Grünwald, V. 67, 82, 128, 152,

153, 266, 308, 410,

507, 898, 486

Grützmann, R.t 761

gryc, t.s 40

Gschwend, J. 945, 1024, 92, 359,

852, 929

Guder, W. 765

Guhlich, M. 34, 78, 101, 227, 292,

713, 747, 757, 776, 584

Gül-Klein, S. 524

Gumpp, J. 492

Günster, C. 515, 531

Günther, M. 635

Günther-Gunkel, M. 177

Guntinas-Lichius, O. 262, 430, 445

Guo, S. 968

Gupta, D. 654, 674

Gupta, Ravi G. 920

Gürgen, D. 201, 209

Gust, R. 984, 983

Guth, D. 66

Gutiérrez-Enríquez, S. 946

Gutsche, K. 63

Gütz, S. 265

Gutzmer, R. 267, 73

Guyot, M. 792

Guzik, Brian W 758

Ha, X. 282

Haag, Georg M. 1040

Haanen, John B.A.G. 690, 700, 158

Haas, B. 52

Haas, D. 785

Haas, P. 705, 717

Häberle, L. 31

Habermann, Felix-Nikolai Oschinka J.

78, 227, 747

Habibzade, T. 85, 357

Hachenberg, J. 629

Hackenberg, S. 739

Hackert, T. 1002

Hackl, M. 198

Häckl, D. 612

Hackshaw, A. 916, 906

Hadaschik, B. 507, 852

Haferkamp, S. 307, 73

Hage, Anna M. 127, 572

Hagemann, C. 485

Hager, T. 416

Hahlweg, P. 312, 418, 626

Hahn, D. 63

Hahn, L. 118

Hahn, M. 735

Hahn, S. 260, 897

Hahne, S. 912

Hahnen, E. 361, 663

Haidenberger, A. 884, 847

Hajduk, E. 793

Hakenberg, O. 21, 22, 23, 880

Hakimhashemi, A. 618

Halfter, K. 311, 539

Halle, L. 454

Hallek, M. 711, 980

Haller, K. 976

Halloul, Z. 609

Hallsson, Lára R. 1016, 947, 955, 1032

Hamacher, R. 486

Hamberg, P. 222

Hamilton, E. 608, 636

Hammel, P. 950

Hammerer, P. 29

Hämmerl, L. 716

Hammling, M. 562

Han, Xi. 990

Handmann, C. 778

Hanenberg, H. 561, 1060

Hanf, V. 751

Hanker, L. 730, 1055

Hansel, A. 445, 680

Hanses, F. 1014

Hanusch, C. 504, 1027

Hapgood, G. 891

Hapke, G. 262

Harbeck, N. 66, 210, 246,

297, 298, 870,

877, 114, 359

Harde, J. 128

Hardes, J. 450

Hardesty, Melissa. M. 636

Harnischfeger, N. 976

Härter, M. 312

Hartkopf, A. 340, 676

Hartmann, Amelie. 679

Hartmann, A. 31, 79, 153, 158,

476, 556

Hartmann, J.T. 410

Hartmann, M. 100

Hartmann, S. 269

Hartmann, W. 345, 450, 749

Hasanov, Mir F. 341

Hasenburg, A. 451, 471, 473, 756

Hassanin, E. 379

Hassel, Jessica C. 73

Hasselmann, K. 537, 555, 779

Hattingen, E. 567

Hattingen, L. 1001

Hatzipanagiotou, Maria E. 611, 903

Hau, P. 613

Haubrock, M. 1

Hauck, T. 607

Hauke, J. 663

Hauprich, J. 914

Hauptmann, M. 269

Hauser, P. 450

Haussmann, A. 197

Hautmann, M. 111, 146, 262, 476

Haveman, L. 450

Haybaeck, J. 404

He, J. 50

He, S. 1002

He, W. 991

He, Y. 53

Headley, D. 436

Hebbel, H. 169, 172

Hecht, G. 354

Hecht, M. 261, 476, 512

Heckelmann, B. 1009

Heesen, P. 450

Heeter, P. 1045

Hege, K. 709

Hegedüs, B. 416

Hegener, P. 429

Heger, T. 946

Hegewisch-Becker, S. 259, 867, 103

Hegg, R. 436

Heibges, M. 397

Heidegger, H. 828

Heidel, Florian H. 323

Heidenreich, A. 661, 698, 701, 708,

711, 715, 980

Heidt, V. 519, 523

Heij, L. 174

Heiland, Dieter H. 140

Heimbach, D. 900

Heimes, Anne-S. 756

Heine, A. 551

Heine, R. 547, 692

Heinemann, V. 297, 537, 555, 359

Heinrich, K. 537, 555

Heinz, J. 593

Heinze, M. 167

Heinzelbecker, J. 556

Heinzelmann, F. 1066

Heinzelmann, J. 853

Heinzelmann-Schwarz, Viola 640, 620

Held, T. 47, 244, 360, 578

Heldmaier, W. 721

Hellmann, M. 218

Hellmis, E. 152

Helmbold, I. 946, 970

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 271

Helweg, M. 679

Hempel, E. 780, 794, 795

Hempel, S. 102

Hengstler, Jan G. 756

Hennig, A. 445

Henrichs, V. 238

Henrique, R. 556

Henschke, S. 370

Hense, J. 20

Henssen, Anton G. 201

Hentschel, L. 134, 635, 702, 804, 486

Henze, L. 1041

Herbaux, C. 891

Herber, M. 267

Herbolsheimer, P. 608

Herbst, R. 267, 410

Herden, J. 661

Herfarth, K. 36, 47, 244

Herhaus, P. 357

Hering-Schubert, C. 211, 103

Herishanu, Y. 166

Herkommer, K. 92, 359, 852

Hermelink, K. 297, 298, 359

Hermes-Moll, K. 519

Hernáiz Driever, P. 673

Hernandez, S. 32

Hernandez-Ilizaliturri, F. 967

Herold, T. 792

Herold, T. 537, 555

Herrmann, M. 864

Herrmann, T. 204

Herschbach, P. 359

Hertel, H. 601, 1015

Hertel, K. 902

Hertenstein, B. 339, 410

Herth, Felix J.F. 413, 482

Hess, Gabriel F. 89, 104

Hess, J. 646

Hester, A. 571

Hettler, M. 292

Heuer, A. 895

Heumann, P. 970

Heuser, C. 161

Heußel, Claus P. 86

Heußner, P. 359

Heydenreich, M. 55, 230, 231, 232

Heyder, U. 547

Heymanns, J. 519

Hietanen, S. 674

Higgins, K. 411

Hilfenhaus, G. 1026

Hilger, C. 397, 889

Hille, A. 101, 227, 757, 776

Hillebrand, Larissa E. 211

Hillemanns, P. 601, 629, 1015, 102

Hillmen, P. 374, 411

Hilser, T. 82, 153, 507

Himmelsbach, V. 425, 443

Hinke, A. 152, 476

Hinkel, A. 82

Hinz, A. 997

Hinz, N. 120

Hipper, A. 135, 280

Hirche, C. 612

Hirschmiller, J. 996

Hoang, B. 341

Hochhaus, A. 100, 323

Hochhauser, D. 950

Hochmair, Maximilian J 908

Höckel, M. 655

Hoechstetter, M. 252

Hoefert, S. 352

Hoegen, P. 578, 851

Hoeller, C. 73

Hoelscher, Arnulf H 767

Hoeltgen, L. 851

Höer, A. 862

Hof, A. 245

Höken, N. 788

Hoknecht, P. 1047

Homann, A. 662

Homann, J. 201, 209, 243, 404, 524

Homann, J. 456

Homann, M. 149

Homann, O. 157, 676

Homann, S. 947, 955, 1016

Homeister, M. 358

Hofheinz, Ralf-D. 1039

Hofmann, Hans-S. 462

Hofmann, Wolf P. 211

Hofmann, Wolf-K.n 12

Hoglander, E. 223

Hohenberger, P. 804

Höhn, P. 814

Hoier, D. 980

Holch, J. 537

Holländer, H. 298

Holland-Letz, T. 36

Hollburg, W. 267

Holleczek, B. 532

Hollnberger, F. 548

Holm, Per S. 1024, 929

Holmberg, C. 876

Hölters, S. 128, 556

Hölting, Tilman L. B. 749

Holtmann, L. 945

Holze, M. 165

Hölzel, M. 79, 551

Hölzle, F. 739

Homayounfar, K. 815

Honisch, E. 740, 785, 745, 561

Honselmann, K. 1009

Höpfner, F. 642

Höpken, Uta E. 296

Horch, Raymund E. 607

Horenkamp-Sonntag, D. 934

Hori, M. 971

Hörmann, N. 984

Horn, Lars-C. 190

Horn, L. 462

Horn, M. 120

Horneber, M. 951, 720

Hornemann, B. 134, 804, 857

Hörner-Rieber, J. 234, 360, 578, 851

Hortobagyi, G. 309

Hotta, K. 908

Hsia, Te-C. 840

Hsu, Chen-J. 323

Hu, N. 942

Huang, J. 374

Huang, L. 709, 208

Huang, Yen-L. 620

Hübbers, Christian U. 446

Hube-Magg, C. 1054, 1029, 1031, 1053

Huber, D. 611

Huber, G. 321

Huber, N. 323

Huber, S. 933

Hübner, Christian A. 323

Hübner, G. 103

Hübner, G. 499

Hübner, J. 686

Hucke, N. 252

Huebner, H. 31

Huebner, J. 100, 453

Huenniger, D. 639

Huerta, M. 715, 661, 708

Huesmann, S. 954

Hughes, C. 281, 282

Hühnchen, P. 159

Hultcrantz, M. 991

Hummel, Horst-D. 280, 1018

Hummel, R. 1009

Hummel, T. 1049

Hummler, S. 669

Hums, Anna-B. 445

Hüneburg, R. 379

Huober, J. 340, 504, 1027, 1059, 676

Hurvitz, Sara A. 309, 936

Huß, A. 341

Hussain, M. 952

Hussein, M. 16

Hutchinson, J. 307

Hutson, T. 308

Ibrahimi, S. 968, 967

Idler, C. 547, 692

Iduna, F. 404

Ihle, P. 934

Ihlow, J. 1026

Ihrig, A. 48

Ihrig, K. 357

Illert, L. 1042

Illes, A. 414

Illmer, T. 476

Im, E. 730

Im, Seock-A. 283

Imkamp, F. 601

Imle, R. 749

Inhestern, L. 871

Inwald, Elisabeth C. 452, 441, 452

Irmer, B. 815

Iro, H. 261, 432, 476

Isfort, P. 119

Isfort, S. 739

Italiano, A. 277

Ito, R. 281, 282

Ivanyi, P. 82, 152, 153, 158,

266, 486

Izbicki, J. 933, 1035

Izquierdo, E. 711

Izutsu, K. 968, 891, 967

J. Hall, M. 950

Jackisch, C. 11, 66, 80, 504, 1027

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index272

Jacob, A. 414

Jacob, Anne S. 339

Jacob, F. 620, 640

Jacob, S. 219

Jacobasch, L. 867

Jaeger, A. 11, 80

Jaehde, U. 635

Jaehn, P. 876

Jaeschke, B. 280

Jafari, A. 921

Jagannath, S. 534, 560, 709, 208

Jäger, B. 785

Jäger, D. 86

Jäger, E. 753, 85

Jäger, M. 586

Jahn, B. 947, 955, 1032, 1016

Jain, R. 446

Jäkel, N. 198

Jakob, Carolin E.M. 1014

Jakob, J. 593, 594, 292

Jakubek, F. 294, 346, 351

Jänicke, M. 67, 135, 211, 246, 259, 280

Janjigian, Yelena Y 1064, 1044

Jann, Johann-C. 12

Janni, W. 11, 80, 340, 656, 658,

954, 1059, 676

Janning, M. 510

Janot-Matuschek, M. 788

Jansen, C. 1037

Jansen, H. 506, 721

Jansen, L. 445, 680

Jansen, L. 358

Janssens, A. 166

Jarczyk, J. 79

Jassem, J. 942

Jechorek, D. 801

Jenner, K. 198

Jensen, Bjoern-E. 1014

Jentschke, E. 386, 419, 485, 1018

Jentschke, M. 102

Jeremias, I. 537, 555

Jerónimo, C. 556

Jerusalem, G. 210

Jeschke, U. 118, 132, 571, 828

Jessen, C. 385

Jewell, A. 1055

Jewell, R. 991

Jhaveri, K. 283, 608

Ji, Jun Ho 908

Ji, M. 374

Jiang, R. 150

Jievaltas, M. 326

Jimenez, B. 990

Jin Hyung, W. 1044

Joachims, J. 156

Jochheim, L. 425

Joedicke, A.s 404

Joedicke, Jara J. 296

Joensuu, H. 952

Johannsen, Lene M. 871

Johannsen, M. 780, 794, 795

John, H. 547

John, J. 751

John, T. 942

John, U. 975, 1022

Johne, A. 370, 840

Johnsen, Steven A. 1

Johnson, Melissa L. 16

Johnston, Patrick B 968, 967

Johnston, S. 436

Joko-Fru, Yvonne W. 716

Jones, B. 829

Jones, David T.W. 829, 628

Joo, S. 1003, 1005

Joos, M. 1065

Joos, S. 692, 720, 951

Jordan, K. 324

Jördens, M. 744

Jost, T. 512, 607

Jou, Ying-M. 971

Joy, S. 547

Jücker, M. 120, 1042

Jucknewitz, R. 621

Juhasz-Böss, I. 341

Jung, A. 537, 555

Jung, L. 659

Jung, P. 1018

Jünger, M. 46

Junghans, K. 198

Junghanß, C. 228, 229, 642

Junker, K. 128, 195, 556

Jurczak, W. 349, 516, 374, 891,

166, 411, 414

Jurgens, H. 450

Jürgensen, C. 855

Just, M. 340, 339

K. Homann, T. 131

Kaaks, R. 852, 946

Kaftan, H. 262, 430

Kähler, Katharina C. 267

Kahlmeyer, A. 233

Kähnert, H. 455

Kailayangiri, S. 31

Kaina, B. 43, 52, 53, 768

Kaiser, C. 522

Kaiser, E. 426

Kaiser, S. 612

Kal, Jörg C. 921, 995

Kalinsky, K. 936

Kalka, C. 621

Kallies, A. 476

Kalogirou, C. 79

Kaltenbach, A. 692, 720, 951

Kaltenecker, G. 269

Kalweit, C. 1049, 1052

Kamal, M. 916

Kambartel, K. 1007

Kamdar, M. 968, 967, 166

Kamio, T. 1074

Kämpfe, D. 869

Kamps, M. 591

Kanerva, J. 450

Kantelhardt, Eva J. 716, 751, 823, 198

Kanz, F. 390

Kao, S. 256

Kapitza, P. 983

Kapp-Schwoerer, Silke 956

Kapur, D. 989

Kapusta, N. 996

Karadeniz Cakmak, G. 269

Karapetyan, Armen R. 223

Karlsson, K. 166

Karsten, Maria M. 127, 572

Kaschdailewitsch, E. 547

Kasper, B. 804, 486

Kasper, S. 276

Kasper-Virchow, S. 20, 344, 752, 792

Katalinic, D. 579, 760

Kater, Arnon P. 411

Kates, Ronald E. 870, 899

Kathmann, L. 706

Katzenmeier, M. 912

Kaumann, P. 566

Kaumann-Guerrero, D. 728

Kaufmann, A. 764

Kaul, D. 884, 847

Kaul, H. 339

Kaur, S. 634

Kawaguchi, Y. 1074

Kayali, M. 663

Kazdal, D. 482, 707

Kazmierczak, M. 374

Keam, B. 308

Keck, Maximilian 686

Keck, T. 1009

Keeton, E. 636

Kehrer, H. 73

Keilholz, U. 260, 524, 563, 1026

Keilmann, Lucia K. 132

Kéïta, M. 823

Keller, D. 502, 649

Keller, M. 788

Keller, M. 159

Keller, R. 1007

Keller, U. 681

Kendel, F. 397, 722, 889

Kengelbach-Weigand, A. 607

Keppler, Bernhard K. 1045

Kerek-Bodden, H. 313

Kerkho, A. 345

Kerkmann, M. 945

Kern, J. 16, 280, 1047

Kern, J. 143, 576

Kersten, J. 727

Kersting, S. 46, 761

Keßler, Almuth F. 485

Kessler, M. 118, 132, 571

Kesting, M. 458, 493

Kesting, S. 673, 356

Ketter, L. 426

Keziban, M. 260

Khalmurzaev, O. 556

Khan, S. 309

Khan, W. 281, 282

Khodamoradi, Y. 1041, 1014

khosravian, M. 403

Kiderlen, Til R. 171

Kieback, E. 681

Kiechle, M. 506, 721, 114, 359

Kiermeier, S. 324, 569

Kieschke, J. 354

Kießig, S. 655

Kim, Dong-W. 840

Kim, Hye R. 989

Kim, Sang-W. 16

Kim, Sung-B. 436

Kim, Yu J. 989

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 273

Kimmig, R. 199

Kim-Wanner, Soo-Z. 300, 398, 675

Kinzel, T. 855

Kirchner, L. 323

Kirchner, T. 537, 555, 749

Kirschner, M. 739

Kiselicki, D. 85

Kislov, N. 33

Kisro, J. 103

Kitz, J. 292, 1077

Klafke, N. 547, 692, 720, 951, 1067

Klamroth, R. 621

Klapdor, R. 601, 629, 1015

Klar, M. 341

Klauschen, F. 537, 555

Klautke, G. 63

Klautke, G. 476

Kleihues-van Tol, K. 515, 531

Kleihus van Tol, K. 1009

Klein, A. 313, 705, 762

Klein, A. 773

Klein, E. 114

Klein, Florian G. 929, 1024

Klein, K. 722

Klein, M. 739

Klein, M. 934

Kleinman, D. 991

Klier, J. 780, 794, 795

Klinghammer, K. 243

Klinkhammer, H. 379

Klinkhammer-Schalke, M. 903, 515, 531,

462, 355, 1009,

441, 492, 452, 1039

Kloess, A. 515

Klopp, N. 416

Kloppe, T. 934

Klotz, Laura V. 413, 707

Klotz, R. 165, 1065

Kluba, T. 410

Kludt, E. 415

Klug, S. 764

Klümper, N. 79, 551

Klußmann, Jens P. 446

Klüter, S. 578

Knapp, I. 724

Knauf, Wolfgang U. 252, 523, 1039

Knebel, P. 1065

Kneis, B. 761

Knobloch, J. 627

Knoefel, Wolfram T 744

Knoop, H. 610

Knop, S. 534

Knopf, A. 454, 646

Knösel, T. 219

Knott, Maximilian M. L. 749

Ko, Yon-Dschun 635

Kobe, C. 339

Kobelt, D. 605

Koch, A. 568

Koch, A. 102

Koch, B. 731

Koch, B. 900

Koch, L. 544

Koch, M. 758

Koch-Gallenkamp, L. 532

Koch-Gromus, U. 616

Köditz, B. 661, 701, 711

Koeberle, D. 103

Koeditz, B. 698, 708, 715

Koepke, Leon-G. 895

Koerber, Stefan A. 36, 852

Koerdel, K. 1

Kohler, R. 381

Kohler, S. 692

Köhler, H. 689

Köhrer, K. 149

Kokh, D. 392

Köksal, M. 921

Kolbe, Ernst W. 170

Kolbe, L. 594

Kolben, T. 132, 571

Kolben, T.s 118, 132, 571

Kolberg, Hans-C. 608, 157

Kolberg-Liedtke, Co. 157

Kölbl, O. 111, 146

Kolk, A. 1024, 929

Kollikowski, A. 735

Kollmar, O. 89, 104

Kollmeier, J. 416, 518, 1047

Kölsch, H. 1032

Kömpel, T. 974, 987

Komrokji, Rami S. 281, 282

Konczalla, L. 933, 1035

Konecny, Gottfried. E. 636

Koneval, L. 233

König, A. 298

König, F. 780, 794, 795

König, Julia Felicitas L. 467

König, L. 47, 234, 244, 360,

500, 578, 851

König, T. 823

Könsgen, N. 914

Kontos, M. 269

Kopp, Hans-G. 486, 410

Köppel, M. 614, 617, 630, 741

Kopyltsov, E. 308, 328, 952

Korach, J. 654

Korshunov, A. 737

Korus, B. 1067

Kosanke, G. 767

Koska, M. 67

Kost, B. 828

Kostbade, K. 276, 344, 752

Koster, J. 201

Kotarac, A. 260, 563

Kotzerke, M. 156

Kouam-Daniel, P. 783

Kouka, M. 430

Kourti, E. 449, 816, 523

Kovac, M. 628

Kovács, L. 180

Kowalski, C. 127

Koziorowski, A. 606, 433

Kozlov, V. 308

Krabbe, Laura-M. 253

Kraeft, Anna-L. 788, 1039, 816, 523

Kraemer, A. 36

Kragl, B. 228

Kramberg, S. 1066

Kramer, M. 134, 702

Krämer, A. 223

Krämer, A. 191, 500

Krämer, A. 380

Krammer-Steiner, B. 103

Krassnig, S. 404

Kratzer, V. 621

Kratzsch, T. 404

Kraus, F. 433

Krause, C. 204

Krause, F. 1

Krause, J. 933

Krause, K. 975

Krause, Luisa C. 134

Kraus-Tiefenbacher, U. 522

Krautz, C. 761

Krawczyk, N. 785

Krawitz, P. 379

Kray, S. 727

Krebs, S. 90

Kreidt, D. 416, 622

Kreissl, S. 610

Krekeler, C. 345, 815

Kreklau, A. 190

Krell, V. 159, 617, 741, 791

Kremeike, K. 634

Kretz, T. 152

Kreuter, A. 267

Kreutz, C. 1040

Kreutz, R. 159

Kreutzer, E. 957

Kreutzer, J. 1071, 1069, 1006, 1075,

1077, 866, 1073

Kreuzwieser, F. 724

Kricheldorf, K. 739

Kriegs, M. 120

Kriegsmann, K. 957

Kriegsmann, M. 413, 707

Krijgsveld, J. 749

Kristeleit, R. 730

Kristiansen, G. 79, 852

Kriston, L. 312

Krivak, T. 636

Kröger, Anne-C. 718

Kröger, B. 547, 692, 720, 951

Kroiher, D. 735

Kroiss, M. 277

Krokenberger, M. 272

Krolo, F. 975, 1022

Krombholz, A. 765

Kronsteiner, D. 191, 500

Krueger, U. 260

Krug, K. 204

Krug, S. 403, 425

Kruggel, L. 245, 246

Krumme, J. 180

Kryachok, I. 414

Kuba, K. 5

Kubuschok, B. 669, 63, 239

Kuczyk, M. 852

Kudak, A. 36, 191, 234

Kueenburg, E. 534

Kufeld, M. 847, 884

Kuhl, C. 119

Kühl, R. 630

Kuhn, Susanne Antje 404

Kühn, F. 127, 572

Kühn, R. 325

Kühn, T. 656, 658, 269

Kühne, F. 1032

Kühne, T. 450

Kuhn-Friedrich, N. 99

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index274

Kulik, A. 405

Kumar, A. 674

Kumar, Y. 933

Kumas, L. 721

Kumbrink, J. 555

Kümmel, S. 870, 877

Kunadt, D. 874

Kuner, T. 1008

Kunitz, A. 486, 410

Kunz, B. 23

Kuon, J. 413, 482, 707

Kupczyk, M. 613

Kupper, A. 492

Küpper-Nybelen, J. 934

Kuptsova-Clarkson, N. 411

Kurreck, A. 624

Kürschner, D. 410

Kurunci-Csacsko, E. 580

Kusch, M. 313, 705, 717,

743, 762, 844

Kuske, A. 306

Kuss, I. 326, 952

Kusterer, L. 1035

Kütting, F. 425

Kutz, Chiara-S. 607

Kuziora, M. 218

Kyjacova, L. 388

L. Kindler, H. 950

La Torre, I. 287

Laack, E. 265

Laban, S. 739, 131, 476

Labouvie, H. 313, 705, 717,

743, 762, 844

Lacko, A. 436

Lai, Z. 218

Lai, Z. 911

Laitman, Y. 361

Lakes, J. 852

Laktionov, K. 16

Lamanna, N. 349, 374, 516

Lambrecht, M. 946

Lammert, A. 143, 576

Landgraf, L. 31

Lang, K. 234, 360, 557

Lang, M. 426

Lange, S. 639

Lange, T. 120

Langer, A. 669

Langer, C. 63

Langer, T. 914

Langer, T. 934

Langhammer, S. 117, 209

Langhans, V. 506

Langheinrich, Melanie C. 761

Lanowska, m. 294, 346, 351

Lantzsch, T. 751

Lanznaster, J. 873, 1014

Lapshyn, H. 1009

Larmann, J. 1065

Larsen, Jeremy T. 534

Lashgari, M. 783

Laskin, J. 277

Lau, A. 499

Laue, K. 276, 344, 752

Laumen, H. 403

Lawler, S. 758

Lawrenz, W. 625

Layer, M. 547, 692

Lazica, D. 42

Le Berre, Marie-A. 326, 327

le Coutre, P. 229

Le Gouill, S. 516

Le Nouveau, P. 691

Le Tourneau, C. 906, 916

Leath III, C. 730

LeBlanc, R. 971

Lebret, T. 327

Lech-Maranda, E. 349

Lechpammer, S. 654

Lederer, J. 758

Ledger, D. 989

Lee, Jae H. 414

Lee, J. 1064

Lee, Jong-S. 920

Lee, Keun-W. 1064

Leerho, S. 170

Leha, A. 1075, 1006, 1069, 866,

1071, 1073, 1, 1077

Lehmann, J. 428, 502, 649

Lehnhardt, M. 251

Lehrach, K. 1066

Lehrke, R. 847

Leibbrand, B. 455

Leibner, M. 204

Leinert, E. 656, 658

Leisegang, M. 681

Leitch, S. 956

Leitsmann, M. 204

Leleu, X. 691

Leleu, X. 971

Lemmen, C. 717

Lendowski, S. 449

Lennartz, M. 1053

Lenton, D. 956

Lenz, G. 345

Lepping, L. 149

Leppla, L. 180

Leprivier, G. 749

Lerchenmüller, C. 259

Letsch, A. 169, 172, 660, 725, 976

Leu, M. 78, 101, 227, 713, 747,

757, 776, 584

Leukers, P. 788

Leuteritz, K. 699

Levchenko, E. 33

Levy, T. 674

Lewis, D. 349, 516

Lewis, K. 516

Lewitzki, V. 262

Li, J. 749

Li, L. 920

Li, R. 952

Li, W. 1003, 1005

Li, Y. 674

Liam, Chong Kim 840

Liang, Ching-Y. 620

Liberati, Anna M. 150

Lichtensteiger, C. 551

Licour, M. 256

Lieb, S. 425

Liebel, K. 143

Liebs, S. 260, 563, 1026

Liersch, R. 33

Liersch, T. 866, 1006, 1069, 1071,

1073, 1075, 1077

Lies, M. 646

Liers, Sven-T. 752, 792

Lihou, Christine F. 335

Lim, Farah L. 16

Limberger, B. 399, 643

Lin, Aimee K. 255

Lin, Nancy U. 210, 309

Lin, Y. 560, 709

Linde, H. 259

Lindenmaier, P. 11, 80

Linderkamp, F. 167

Lindert, T. 788

Lindig, A. 312, 418

Lindley, A. 335

Lindner, L. 219, 486

Lindörfer, D. 947, 955, 1016

Lindsay, J. 150

Ling, T. 991

Lingohr, P. 921

Lingua, A. 942

Link, H. 1036

Link, T. 504, 1027, 1050

Linnebacher, M. 535, 718

Lipfert, Lisa-M. 662

Lippach, K. 49

Lippert, H. 742, 759

Liu, B. 10

Liu, Fei Fei 968

Liu, W. 690, 700, 989

Liu, X. 486

Liu, Y. 956

Livingstone, E. 267

Lobo, J. 556

Loeer, C. 735

Loertzer, H. 556

Loges, S. 369, 510

Löhberg, C. 676

Löhden, I. 238

Lohmann, A. 614

Lohmüller, L. 720, 951

Lohneis, P. 428

Lohse, S. 556

Loi, S. 283, 608, 1027

Loibl, S. 309, 504, 1027, 114, 936

Loirat, D. 936

Lonial, S. 534, 709, 208

Loong, H. 255

Loosen, S. 744

Lopez, Pilar G. 989

Loquai, C. 73

Lorch, A. 152, 158

Lordick, F. 699, 787, 1023,

1064, 1062

Lorenz, A. 66

Lorenz, A. 548

Lorenzen, S. 357

Lorocca, A. 150

Lorusso, D. 1050

Losa, F. 223

Losem, C. 574

Löser, H. 428

Löser, H. 810

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 275

Loskutov, J. 325, 366, 684, 718

Lösse, V. 575, 987

Lowinus, T. 307

Lu, S. 942, 840

Lübke, Andreas M. 1053

Ludescher, M. 748

Ludwig, A. 399, 643

Ludwig, C. 198

Ludwig, S. 576, 143

Luedde, T. 744

Luerken, L. 813

Luft, A. 16

Lüftner, D. 66

Lugnier, C. 523, 788, 1039, 816

Lüke, C. 156

Lunning, M. 968, 967

Lupinacci, L. 920

Lüpkes, C. 934

Lurati, Magalie C. J. 1029, 1031

Lusky, F. 482

Lutz, R. 458, 493

Lutze, S. 46

Luz, M. 326

Lynch, C. 309

Lyros, O. 697, 399, 643

Lysak, D. 414

M. Kraus, J. 131

M. O‘Reilly, E. 950

Maag, Teresa E. 747, 757

Maas, L. 625

Maas, L. 502

Maas, V. 136, 659, 575

Maasberg, M. 82

Maass, Kendra K. 829

Maass, N. 169, 172

Maatoug, Y. 701

Maatouk, I. 324, 360, 569

Macarulla, T. 950

Mach, P. 199

Machmer, T. 191

Mackensen, A. 31

Maenz, M 1047

Maghnouj, A. 897

Mahler, C. 692, 720, 951

Mahn, R. 921, 995

Mahner, S. 118, 571, 114, 359,

298, 828, 132

Mai, K. 159

Maier, A. 1030

Maier, S. 297

Maintz, C. 82, 245

Mairinger, E. 199, 416, 518, 622

Mairinger, Fabian D. 199, 416, 518, 622

Mairinger, T. 518, 416

Maj, C. 379

Majchrzak-Stiller, B. 814

Makowski, M. 852

Maktabi, M. 689

Malinka, T. 624

Malinowska, I. 674

Mallm, Jan-P. 737

Maloney, D. 967

Mamlouk, S. 325

Man, S. 562, 727

Mańczak, A. 921

Mandelkow, T. 1054, 1053, 1031, 1029

Mandrella, M. 594

mangler, m. 294, 346, 351

Manier, S. 560

Mann, H. 908

Mann, J. 731

Mann, M. 929

Mannewitz, M. 132, 571, 118

Mannsmann, V. 171

Mansmann, U. 621, 947, 955, 1016

Mansy, T. 868

Mantovani, E. 281, 282

Mantsopoulos, K. 261

Mantwill, K. 929, 1024

Manz, K. 862

Mänz, M. 152, 1007

Marass, F. 745

March, C. 604

Marchetto, A. 749

Marheinecke, Corinna S. 449

Maria, W. 21

Mariani, M. 151

Marinova, M. 995

Märkl, B. 669

Markus, M. 594

Markus, P. 276, 344, 752

Marmé, F. 504

Maroto, P. 308, 158

Marquardt, Jens U. 443

Marschall, U. 934

Marschner, N. 67, 246, 259

Martel, J. 268

Marten-Mittag, B. 359

Martens, U. 67, 166, 906, 916

Marti Grifol, C. 697

Martin, M. 436

Martinez-Marti, A. 33

März, M.l 146

Maschmeyer, G. 262

Masini, C. 222

Maßmann, M. 344, 752

Matasar, M. 891

Mathies, V. 961, 1056

Mathilakathu, A. 416, 622

Mathys, B. 354

Mato, Anthony R. 516, 411, 349

Matsuda, T. 117

Matthes, B. 964

Matthes, H. 299

Matthews, C. 730, 1050, 1055

Matulonis, U. 654

Matveev, V. 556

Maulbecker-Armstrong, C. 940, 941

Maurer, G. 567

Maurer, J. 931

Maurer, L. 159

Mauz, Paul-S. 63

Mavroeidi, Ilektra-A. 792

Mawrin, C. 474

May, P. 379

May, S. 167

Mayer, A. 1057

Mayer, B. 586

Mayer, F. 410

Mayer, J. 374

Mayr, A. 379

Mayr, D. 828, 114

Mazieres, J. 868

Mboni Johnston, Isaac M. 490

McAdoo, W. 1064

McCormick, C. 674

McDonald, F. 256

McKeown, A. 991

McKiver, Mihaela P. 971

McNally, V. 33

Medic, N. 16

Mehlis, K. 961, 415

Mehnert, A. 1062

Mehnert-Theuerkauf, A. 5, 610, 616,

857, 1030

Mehta-Shah, N. 891

Meier, F. 73, 456

Meier, I. 934

Meier-Stiegen, F. 676

Meiler, J. 152, 153

Meinhardt, G. 1074

Meisel, Hans-J. 474

Meiss, F. 307

Meissner, Valentin H. 92

Meister, M. 482

Meister, S. 118, 132, 571

Meixner, E. 234, 851

Melcher, I. 410

Melichar, B. 308

Mellado, B. 158

Melling, N. 933, 1035

Menck, K. 345, 808, 815

Mende, B. 344, 752

Mende, S. 36

Mendes Wefelnberg, M. 772

Mendrina, T. 1045

Meneceur, S. 149

Menevse, Ayse N. 613

Menezes, D. 287

Menezes, J. 942

Menold, N. 1056, 961

Menrath, I. 673

Mentrup, S. 660, 725

Mercade, Teresa M. 714

Merkel, S. 864

Merkelbach-Bruse, S. 912

Merker, S. 510

Merle, P. 32

Mertens, I. 547

Mertins, P. 260, 524, 605

Merzenich, H. 997

Mess, Elisabeth V. 180

Messina, C. 902

Metz, M. 152

Metzeler, K. 537

Metzergoth, G. 12

Meye, H. 522

Meyer, C. 94, 1022, 975, 562

Meyer, F. 604, 609, 736, 738,

742, 759, 781,

793, 801, 809

Meyer, J. 829

Meyer, M. 86

Meyer, M. 618

Meyer, N. 914

Meyer, O. 869

Meyer, T. 1

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index276

Meyer-Knees, J. 624

Meyer-Schwickerath, C. 321

Mezger, N. 716, 823

Michels, B. 1006, 1071

Michels, S. 912

Michielin, O. 73

Michl, P. 403

Micke, O. 410

Mielke, S. 690, 700, 967

Migliorino, Maria R. 868

Migotti, R. 605

Mihaljevic, A. 165

Mikesch, Jan-H. 268

Mileshkin, L. 223

Miller-Phillips, L. 537

Mink, J. 556

Minner, S. 1031, 1053

Minto, Carrie-A. 731, 735, 826

Miranda, P. 411

Mirza, M. 654

Misiak, D. 403

Miskic, M. 327

Miteva, D. 281, 282

Mitter, S. 132, 571

Mix, M. 591, 513

Mizutani, H. 942

Mocek, A. 862

Moch, H. 223

Modi, A. 1001

Modrok, M. 568

Mogwitz, R. 639

Mohammad, Nadia H. 1064

Mohr, P. 267

Mohr, R. 425

Mohr, T. 1045

Möhring, C. 921, 995

Mok, T. 16

Mokritzkij, M. 524

Moldenhauer, G. 86

Molena, D. 1044

Möller, K. 1054

Momburg, F. 86

Monin, M. 921

Monk, Bradley J 654, 674

Mönnigho, U. 519

Montesa Pino, A. 952

Montesinos, P. 287

Montheard, S. 968, 967

Moore, K. 654

Moore, Richard. G. 674, 636

Morakis, P. 177, 390, 392

Moran, D. 117

Moratin, J. 360

Morawietz, C. 321

Moreau, P. 150, 709, 971, 208

Morgan, M. 629

Moritz, Rose C.K. 198

Moritz-Tugral, R. 801

Mornex, F. 256

Morris, P. 504

Morschhauser, F. 891, 967

Mörtl, B. 779

Moser, K. 940, 941

Motzer, R. 308

Moy, B. 553

Muacevic, A. 847, 884

Muders, M. 79

Muegge, Lars-O. 229

Muehlan, H. 655

Muehlensiepen, F. 167

Mueller, Daniel W. 85

Mueller, L. 132

Muenst, S. 89

Mühlberger, N. 947, 955, 1032, 1016

Muley, T. 413, 482, 707

Müller, A. 430

Müller, A. 128

Müller, C. 426

Müller, C. 59, 425

Müller, G. 381

Müller, H. 398

Müller, H. 610

Müller, Jan H. 1029, 1031

Müller, J. 1040

Müller, L. 571

Müller, L. 561

Müller, L. 676, 152, 67

Müller, S. 261, 432

Müller, T. 635

Müller, T. 814

Müller, V. 267

Müller, V. 11, 66, 80, 210, 283,

340, 954, 676

Müller-Huesmann, H. 103, 265, 266, 63

Müller-Nordhorn, J. 618

Müller-Schuchardt, A. 456

Mullins, C. 535

Mumm, F. 297, 359

Munhoz, E. 891

Munir, T. 166

Munoz, M. 436

Munshi, Nikhil C. 709, 208

Münstermann, J. 686

Münter, M. 262

Munugalavadla, V. 166

Muraro, Manuele G. 104

Murawa, D. 269

Muro, K. 1044

Murthy, Rashmi K. 309

Murua Escobar, H. 642

Musa, J. 749

Mustafa, B. 897

Muster, J. 78, 227

Musuraca, G. 414

Müther, M. 943

Mutsaers, P. 968, 967

Mykhalska, L. 891

Naendrup, Jan-H. 767

Nagels, K. 391

Nano, D. 90

Napp, J. 293

Narasimhan, H. 931

Nath, A. 416

Nathrath, M. 628

Nauck, F. 757

Naumann, C. 198

Naumann, P. 47, 244

Nawroth, R. 1024, 929

Nees, J. 569

Negrier, S. 158

Negro, A. 1044

Nekljudova, V. 1027, 114

Nel, I. 190

Nennecke, A. 238, 532

Nestler, T. 701, 711

Neubauer, A.s 726

Neubauer, H. 380, 405, 590,

740, 745, 748

Neuberger, P. 547

Neubert, S. 386

Neuhaus, B. 102

Neumann, C. 624, 1026

Neumann, Ulf P. 627

Neumann-Stern, C. 134

Neuser, P. 300, 398

Neustadt, A. 198

Neuwirth, E. 873

Ng, F. 621

Nguemeni, C. 385

Nguyen, Tuong V. 534

Nguyen, Van A. 544

Nicholas, A. 32

Nickel, E. 111

Nicol, D. 701

Nicolay, Nils H. 140, 191, 454, 460, 513, 646

Niederacher, D. 380, 405, 561, 590,

740, 745, 748, 785

Niegisch, G. 82, 149

Niehues, T. 625

Niels, T. 20, 617, 741, 767, 773

Niethard, M. 366, 678

Nietzio, A. 724

Niikura, N. 283, 210

Niinikoski, L. 269

Nikendei, C. 360

Nilius, G. 606, 433

Nishio, M. 920

Nitsch, T. 873

Noack, B. 494

Noething, C. 586

Nogova, L. 912

Nolting, J. 23, 21

Nöpel-Dünnebacke, S. 523, 788

Nordt, C. 46

Nothacker, M. 914

Nöthen, M. 379

Noujaim, J. 690, 700

Novello, S. 989

Novotny, W. 374

Nowak, A. 198

Nowak, D. 12

Nowicki, M. 758

Nowotny, R. 697

Nuhn, P. 79

Nunez-Lopez, M. 620

Nusch, A. 67, 246, 867

Nyanchama, M. 716

O’Byrne, Kenneth J. 920

O’Shaughnessy, J. 936

Oakman, C. 309

Oaknin, A. 730, 990, 1055

Oberhoer-Fritz, R. 356

Oberic, L. 891

O‘Brien, S. 374, 411

O‘Cearbhaill, R. 674

Ochsenreither, S. 370, 681

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 277

Ockert-Schön, F. 655

Odenthal, M. 817

Oechsle, K. 634, 976, 1062

Oehme, I. 749

Oei, Shiao L. 299, 964

Oertel, M. 268, 573

Ogasawara, K. 967

Ogrodnik, Simon J. 482

Oh, Do-Y. 950, 1064

Oh Park, J. 950

Oh-Hohenhorst, Su J. 972

Ohlmann, C. 881, 945

Ohlrogge, C. 472

Okera, M. 436

Okonechnikov, K. 737

Oksentyuk Polyakova, T. 604, 781

Oksuzoglu, B. 436

Oliveira, M. 936, 309

Olmos, M. 493

O‘Malley, D. 674, 730, 1055

On, J. 405

Ooms, M. 739

Opalinska, J. 991

Oriol, A. 150, 534, 709

Orth, Martin F. 749

Orthmann, A. 404

Ortiz, J. 328

Ortmann, O. 452, 611, 441, 903, 347

Ortner, P. 288, 298

Oschwald, V. 136, 575, 659, 974, 987

Oscroft, E. 210

Osterland, M. 388

Ostermann, H. 369, 621

Osumi, H. 260, 563

Oswald, H. 744

Oswald, J. 462

Otremba, Burkhard J. 239

Otten, S. 136, 974, 987

Ottensmeier, C. 131

Otto, G. 370

Otto, R. 809, 759

Ou, X. 950

Oubaid, N. 634

Ouedraogo, N. 940, 941

Oughton, J. 902

Ouyang, Q. 436

Overbeck, T. 370

Overheu, O. 449

Overkamp, F. 385, 553

Oya, M. 151, 308

Oyelami, F. 329

Ozga, Ann-K. 731

Özgüroğlu, M. 908

Pabst, T. 339

Pachmayr, E. 524

Pacíco, C. 1037

Paenholz, P. 701

Pagel, John M. 349, 516

Paik, Paul K. 370

Pajtler, Kristian W. 829, 737

Pallasch, C. 711

Palomba, M. Lia 516

Pamuk, A. 810

Panic, A. 158

Panse, J. 218

Panse, J. 1041

Panse, J. 116, 911

Pantel, K. 954, 1035, 676

Papadopoulos, N. 294, 346, 351

Papazisis, K. 436

Pardo, L. 566

Park, Chandler H. 952

Park, K. 255

Parks, D. 1050

Park-Simon, Tjoung-W. 436

Parnis, F. 952

Pascher, A. 345

Passlick, B. 135

Passmann, E. 912

Patel, Manish R. 349, 516

Patel, N. 690, 700

Patel, P. 709

Patel, R. 690, 700

Patre, M. 283

Pauer, A. 355, 441, 492, 903, 452

Pauge, S. 961, 1056

Pauker, W. 42, 109, 186, 479

PAUL, A. 276, 344, 752, 792

Pauli, C. 223

Pauligk, C. 357

Pausch, Thomas M. 1002

Pawandenat, C. 874

Pawlak, M. 590

Pawlowska-Phelan, D. 862

Paz-Ares, L. 116, 868, 908,

920, 942, 911

Pazgan-Simon, M. 714

Pedersoli, F. 119

Peeck, M. 345, 815

Peifer, M. 502

Peintinger, F. 269

Péko, Jean-F. 716

Peluso, T. 150

Pelzer, U. 624, 1026, 1049, 1052

Penkov, K. 989

Pereira, P. 211

Perez, D. 933

Perez, Ignacio D. 868

Perez, L. 916

Pérez-Fidalgo, Jose-A. 674

Perez-Hernandez, D. 605

Perkhofer, L. 1003

Perl, T. 529

Perleberg, C. 118

Perner, F. 323

Perrakis, A. 809

Perret, C. 906, 916

Perrot, V. 222

Peschel, S. 751

Peters, C. 356

Peters, I. 814

Peters, I. 852

Peters, S. 46

Peters, S. 16, 337, 218, 256

Petersen, M. 781

Petersen, V. 280

Petricoin III, E. F 1005, 1003

Petrova, E. 1009

Petzsch, P. 149

Pezzutto, A. 681

Pfänder, S. 449

Pfeilstöcker, M. 287

Pster, K. 1059

Pster, Stefan M. 829, 749, 201, 737

Paume, A. 524, 684

Pfohl, U. 325, 718

Pföhler, C. 267, 648

Pförtner, Timo-K. 44

Phan, See-C. 936

Philipp, Lisa-M. 179, 490, 1001

Philipp, R. 871

Piccart-Gebhart, M. 936

Pichler, T. 297, 359

Piee-Staa, A. 52

Pieper, D. 914

Pietzner, K. 291, 302

Pigorsch, S. 359

Pilarsky, C. 678

Pink, D. 702, 804

Pinter, M. 425, 443

Pinto, A. 891

Pinto, D. 269

Pirker, C. 1045

Pirmorady, A. 159

Piscuoglio, S. 89, 104

Pishvaian, Michael J 1003, 1005

Piskorski, L. 578

Piso, P. 355, 1039

Placke, Jan-M. 307

Plathe-Ignatz, C. 634

Platzbecker, U. 5, 281, 282, 610, 956

Ploner, T. 862

Pluetschow, A. 339

Plum, Patrick S. 1002

Pluta, A. 414

Poehler, M. 751

Pogorzelski, M. 276, 344, 752

Poltoratskiy, A. 908

Polyakov, S. 326

Polzer, B. 380

Poole, L. 16, 218

Popat, R. 534

Popp, F. 428

Popp, I. 454

Popp, O. 524, 605

Popper, U. 103

Porat, Y. 460

Porst, J. 159, 791

Porta, C. 308

Poschke, I. 482

Possiel, J. 101, 713, 776

Pothuri, B. 730, 1055

Pott, C. 638, 679

Pottho, K. 211, 245

Powers, B. 690, 700

Powerski, Maciej J. 59

Powles, T. 308

Prager, G. 867, 103, 335

Pramatarov, R. 1008

Prate, K. 874

Pratschke, J. 624, 1026

Preissler, Bastian I. 198

Prenzel, R. 694

Press, J. 730

Pretzsch, E. 219

Preugszat, E. 428, 649

Previtali, A. 968, 967

Priesch-Grzeszkowiak, B. 783

Priese, J. 445

Priselac, K. 1037

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index278

Pritzkuleit, R. 532

Procopio, G. 222, 308

Proescholdt, M. 815

Prokakis, E. 588

Prokop, A. 136, 673

Pross, T. 127, 572

Protsenko, S. 942

Prugger, V. 351, 346

Pryalukhin, A. 556

Przybylla, R. 535

Ptok, H. 738, 809, 736

Ptok, J. 561

Pukrop, T. 815

Pullankavunkal, J. 346, 351, 294

Püllen, L. 507

Punie, K. 936

Puranachot, P. 829

Puri, T. 255

Püschel, L. 660

Qian, Y. 10

Qiu, L. 374

Quaas, A. 428, 446, 502, 649, 810, 812

Quaester, S. 179, 490

Quast, Daniel R. 449

Quiering, C. 1004

Quinn, D. 151

Raab, Marc-S. 971

Raab, M. 565, 580

Rabe, A. 386, 419, 485, 1018

Rachow, T. 100

Raciborska, A. 450

Rack, B. 340, 954, 1059, 676

Rademacher, A. 737

Radtke, Jan P. 852

Radulovic, I. 561

Radziwill, R. 754

Raem, Arnold M. 170

Rafei-Shamsabadi, D. 307

Rayan, Mohammad-R. 85, 152

Rafyian, R. 82

Rahat, Michal A. 329

Rahn, Anne C. 660, 725

Rahn, S. 179

Rai, S. 891

Raja, R. 218

Rajagopal, R. 956

Raje, N. 560, 709, 208

Ramaker, K. 269

Ramalingam, S. S. 337, 920

Ramanathan, S. 956

Rambaldi, A. 709

Ramos, J. 309

Ramroth, H. 252

Rancati, T. 946, 970

Ranft, A. 450

Ranogajec, I. 579

Rapp, M. 398

Räpple, S. 903

Rascon, J. 450

Rasenberger, B. 768

Rath, Hilke M. 976

Rattay, T. 946

Rau, B. 388, 524

Rau, Bettina M. 492

Rauch, J. 359

Raue, Jan S. 1030

Rawluk, J. 218

Reck, M. 135, 868, 920, 942, 1007, 1047

Reder, H. 446

Reece, D. 709, 208

Reeh, M. 1035

Reetz, K. 1023

Reeves, J. 436

Regenbrecht, C. 325, 366, 524,

678, 684, 718

Regenbrecht, M. 366

Regnery, S. 47, 191, 244, 360, 578

Rehm, A. 296

Rehms, R. 947, 955, 1016

Reich, F. 94

Reich, V. 855

Reichelt, R. 306

Reichenbach, F. 103, 260, 867

Reichert, D. 67

Reinacher-Schick, A. 449, 523, 788, 799,

816, 950, 1039

Reinert, S. 352

Reinhard, C. 325, 366, 684

Reinhardt, D. 2, 625, 1060

Reinhardt, F. 745

Reinhold, T. 159

Reinisch, M. 504, 309, 1027

Reinmuth, N. 16, 370, 868, 908,

942, 1007

Reinwald, M. 171

Reis, H. 507, 518

Reis, Joschua M. 419

Reiser, M. 135, 259, 869

Reißig, T. 792

Reitz, M. 974, 987

Relógio, A. 302

Rémy, R. 44

Ren, H. 219

Rengsberger, M. 100

Reni, M. 950

Renkamp, C. Katharina 578

Retz, M. 945

Reulen, Hans-J. 943

Reuter, B. 63

Reuter, H. 857

Rexer, H. 29

Rey, J. 504

Reyes, F. 942

Rezai, M. 429

Rhein, S. 243, 681

Rhiem, K. 44, 1027

Ribaut, J. 180

Richards, Elisabeth C. 335

Richardson, D. 636

Richardson, P. 150, 534, 971

Richter, D. 699

Richter, L. 961, 1056

Richter, P. 986

Richter, R. 716

Richter, S. 804, 486

Richter, T. 655

Richtig, E. 73

Ridwelski, K. 759, 793

Ried, K. 611

Riedel, R. 912

Rieder, N. 976

Rieken, S. 34, 47, 78, 101, 227,

244, 360, 500, 713, 747,

757, 776, 583, 584

Riemenschneider, Markus J. 613

Riera Knorrenschild, J. 726, 63

Ries, J. 458, 493

Rieser, T. 299

Riess, H. 624

Riethdorf, S. 676, 1035

Rimmer, N. 620

Rinnerthaler, G. 66

Rippe, K. 737

Rippke, C. 578

Ristau, J. 578, 36

Risueño, A. 287

Ritschel, Maria-L. 682

Ritter, C. 655

Ritter, M. 79, 551

Ritter, T. 1006, 1069, 1071, 1073, 1077

Rittmeyer, A. 1007

Rivandi, M. 380, 590, 740, 745

Rizvi, N. 218

Robak, P. 150

Robbins, Scott H. 1044

Robinson, B. 277

Robold, T. 462

Roboz, G. 287

Robrahn, L. 627

Roca Ripoll, B. 611

Röcken, C. 209

Roderburg, C. 744

Rodriguez-Lopez, K. 308

Rodriguez-Otero, P. 534, 560

Roeker, Lindsey E. 349

Roeper, J. 694, 706, 712

Rogahn, J. 228

Rogge, T. 808

Roggendorf, S. 499

Roghmann, F. 79

Rohrer, P. 544

Röhrle, J. 344, 752

Rohrmus, C. 613

Roll, S. 159

Roll, W. 943

Rolland, F. 308

Rolles, B. 739

Rolo, D. 99

Romero-Perez, L. 749

Ronellentsch, U. 593

Roob, D. 851

Roos, F. 128

Rose, M. 159, 291

Rosé, C. 260

Rose-John, Stefan. 1

Rosenstein, B. 970, 946

Rosenwald, A. 339

Rosery, Vivian K. 344, 276, 752

Ross, G. 283

Ross, Jerey S. 223

Rossdam, C. 620

Rössig, C. 31

Rößler, M. 515, 531

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 279

Roth, J. 627

Rotmann, A. 769

Rotter, N. 576, 143, 262

Rottey, S. 158

Rowe, E. 560, 208

Rubio, Isabel T. 269

Rübner, M. 31

Ruckes, C. 1057

Ruckhäberle, E. 785, 676

Ruckriegl, S. 588

Rudert, M. 410

Rudin, Charles M. 911

Rudolph, I. 615

Rueegg, Corina S. 625

Ruescho, J. 810

Rueß, D. 847

Ruf, F. 269

Ruf, J. 513, 591

Ruge, M. 847

Rugo, H. 936

Rühl, R. 568

Rühle, A. 140, 454, 460, 513, 646

Rühlmann, K. 537, 555

Ruhnke, T. 531

Rummel, M. 252

Rummeny, E. 852

Runnebaum, Ingo B. 662, 680

Rupp, R. 261

Ruscica, D. 1044

Rüthrich, Maria M. 1014, 1041

Rutty, D. 1036

Ryabov, V. 12

Saad, F. 952

Saalfeld, F.C. 510

Saal, J. 79, 551

Sabatier, R. 730, 1055

Sadeghlar, F. 921, 995

Sadewasser, K. 1022

Sadjadian, P. 1007, 1047

Safaei, R. 523, 788

Sagasser, J. 340

Sahi, D. 980

Sahlmann, Carsten-O. 1077, 1069

Sahm, F. 829

Saito, H. 16

Saito, K. 308

Saito, T. 117

Sakai, H. 370

Salameh, R. 593

Salat, C. 306

Salchow, J. 731, 735, 826

Salem, R. 32

Salgueiro, L 510

Salim, Hizirwan S. 119

Sallach, N. 169, 172

Salles, G. 891

Salm, H. 702

Salmi, T. 374

Salomon, Arne G. 171

Salwender, H. 991

Samatin, Fana-L. 198

Samouelian, V. 730, 990, 1055

Sánchez, José Garcia 868

Sanchin, L. 474

Sandrini, E. 851

Sanford, J. 560

Sangha, R. 920

Sanhaji, M. 565, 580

Sankarasubramanian, S. 678, 718

San-Miguel, J. 150, 208, 709, 971

Santini, V. 281, 282

Sarapohja, T. 326, 328

Sarria, Gustavo R. 921

Sastre, A. 749

Saternus, R. 648

Sätzler, R. 1066

Sauer, C. 360

Sauer, G. 1041

Sauer, R. 366

Sauer, S. 957

Sauerland, S. 1032

Sauter, G. 1053, 1031, 1029

Sautier, L. 616

Sawyer, W. 256

Schaaf, M. 85

Schaal, H. 561

Schad, F. 299, 497, 964

Schad, Paulina S. 829

Schadendorf, D. 73, 267, 456

Schaefer, C. 914

Schaefer, N. 764

Schäfers, M. 943

Schäeler, N. 352

Scharath, N. 753

Schagh, D. 446

Schalk, E. 1041

Schaller, J. 506

Schambach, A. 629

Schanz, J. 1071, 1075, 1073

Schaper, T. 429

Schatz, S. 554

Schaub, V. 339

Schauberger, G. 764

Schauer, D. 912

Scheel, A. 810

Scheer, M. 912

Scheibenbogen, C. 159

Scheil-Bertram, S. 181

Scheiner, B. 425, 443

Schellenberger, B. 161

Schellhorn, H. 862

Schenk, J. 773

Schenk, M. 1002

Schenker, M. 436

Scheper, J. 512

Scherer, Laura-S. 426

Scherer, A. 983

Schetelig, J. 874

Scheuring, A. 1069

Scheuring, U. 218

Schichor, C. 847

Schick, B. 648

Schieferdecker, A. 976

Schiele, S. 92

Schierle, K. 689

Schieron, M. 724

Schiewer, V. 313, 705, 717, 743,

762, 844

Schildhaus, Hans-U. 276, 344, 507,

752, 792, 815

Schildmann, J. 198, 523, 799, 816, 1039

Schilling, G. 616

Schilling, J. 11, 80, 288

Schilling, O. 586

Schimanski, Carl C. 368

Schimmelpfennig, J. 621

Schimmöller, L. 852

Schindlbeck, C. 114

Schindler, C. 612

Schindler, H. 482

Schinke, T. 120

Schinköthe, T. 66, 870, 877, 899

Schirmer, M. 101, 34

Schirmer, Markus A. 78, 227, 713,

747, 757, 776, 584

Schjesvold, F. 150

Schlack, K. 253

Schlag, R. 869

Schlaiß, T. 656

Schlamann, M. 446

Schlampp, I. 36

Schlander, M. 415

Schlecht, S. 386

Schlecht, U. 902

Schleicher, Julia T. 426

Schlemmer, H. 852

Schlenska-Lange, A. 67, 211

Schlesinger-Raab, A. 311, 539

Schlesner, M. 669

Schliephake, H. 329, 566

Schlößer, Hans. A. 428, 502, 649

Schmalfeldt, B. 312

Schmall, A. 327

Schmautz, M. 708

Schmeling, B. 547

Schmid, I. 356

Schmid, Kurt W. 199, 276, 344, 416,

507, 518, 622, 752

Schmid, P.r 608

Schmidinger, M. 151

Schmidt, A. 870, 877, 899

Schmidt, D. 631

Schmidt, H. 198, 499

Schmidt, L. 197

Schmidt, M. 66, 340, 756

Schmidt, R. 689

Schmidt, S. 663

Schmidt, T. 1002

Schmidt, T. 169, 172

Schmidtmann, I. 368

Schmidt-Wolf, I. 635

Schmiedeknecht, A. 262

Schminke, B. 566

Schmitt, D. 78

Schmitt, J. 515, 523, 531, 799, 804, 1039

Schmitt, N. 12

Schmitt, T. 1041

Schmitz, J. 912

Schmitz, M. 445, 680

Schmoeckel, E. 132, 571, 118

Schmolling, J. 663

Schmutz, G. 429

Schmutz, M. 669

Schmutzler, Rita K. 361, 663, 44

Schnabel, A. 1023

Schnabel, M. 82

Schnaubelt, R. 522

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index280

Schneeweiss, A. 340, 1027, 1040, 676

Schneider, C. 642

Schneider, D. 673

Schneider, F. 522

Schneider, Marc A. 482, 707

Schneider, M. 1002

Schneidewind, L. 23

Schnell, K. 118

Schnell, O. 140

Schnell, R. 245

Schnelzer, A. 114

Schnitzler, P. 482

Schnöder, Tina. M. 323

Schochter, F. 340

Schoenfeld, Adam J. 690, 700

Schoenhacker-Alte, B. 1045

Schoer, O. 515, 523, 531, 799, 1039

Schöski, P. 486

Scholl, I. 312, 418, 626

Scholz, C. 171

Schömig-Markiefka, B. 810, 812

Schönburg, S. 198

Schönfelder, R. 780, 794, 795

Schönherr, C. 82

Schostak, M. 152, 326, 898

Schott, S. 569

Schrader, Andres J. 253

Schran, S. 428

Schrauder, Michael G. 269

Schröder, B. 288

Schröder, J. 103, 211, 280

Schröder, J. 780, 794, 795

Schröder, U. 262

Schröder, W. 810

Schrodi, S. 441, 114

Schub, N. 679

Schubert, J. 485

Schubert, K. 47, 244

Schubert-Fritschle, G. 311, 539, 114

Schuhmacher, L. 855

Schuler, Markus K. 702, 804, 486, 635

Schuler, M. 20, 276, 337, 344,

507, 518, 752, 792

Schuler, P. 131

Schuler, U. 134

Schüler, K. 751

Schüler-Toprak, Su. 347

Schulte, Johannes H. 201

Schultheis, A. 446

Schultheiss, M. 425

Schultz, A. 238

Schultze-Mosgau, S. 430

Schulz, C. 116, 911

Schulz, Hans-U. 801

Schulz, H. 137, 634

Schulz, L. 170

Schulz, M. 621

Schulze, M. 82

Schulze, S. 198, 200, 229

Schulz-Wendtland, R. 31

Schumacher, B. 276, 344, 752

Schumann, C. 265

Schündeln, M. 561

Schunn, F. 36, 191, 500

Schuster, A. 117

Schuster, J. 432

Schuster, S. 385

Schuster, Stephen J. 349

Schütt, P. 152

Schütte, K. 134, 635

Schütte, W. 33, 99

Schüttfort, Victor M. 972

Schütze, F. 385

Schütze, S. 662

Schwab, R. 451, 471, 473

Schwamborn, K. 272

Schwarz, N. 829

Schwarzenbach, C. 768

Schweiger-Eisbacher, C. 524

Schwenk, B. 1066

Schwentner, L. 656, 658

Schwinn, T. 996

Schwitter, M. 66

Scott, E. 991

Scriba, D. 694

Sebastian, M. 135, 280, 694,

1007, 1047

Sebens, S. 179, 209, 490, 1001

Seehausen, A. 642

Seemann, C. 179, 490

See-Zepeda, W. 287

Segeth, F. 929, 1024

Segmüller, T. 724

Sehn, Laurie H. 891

Sehouli, J. 159, 291, 302

Seibold, P. 970, 946

Seidel, N. 874

Seif, A. 292, 1069

Seif Amir Hosseini, A. 1077

Seifert, M. 40

Seifert, M. 799

Seiler, S. 1027

Seitz, S. 611, 903

Seiz, E. 143

Seliger, B. 128

Selle, F. 674

Semrau, S. 261, 476

Sender, A. 699

Sendler, A. 1007

Senft, C. 568

Senger, C. 847

Seraj, J. 1074

Seraphin, Tobias P. 716

Serrano, A. 410

Servant, N. 916

Seuerlein, T. 714

Seymour, John F. 411

Shadman, M. 374

Shah, M. 277

Shah, N. 709

Shah, Nirav N. 349, 516

Shah, R. 413, 482, 707

Shaheen, M. 157

Shahin, M. 674

Shao-Weng Tan, D. 255

Sharan, K. 950

Sharman, J. 166, 891

Shehu, E. 499

Shen, L. 1074

Sherman, E. 277

Shi, L. 337

Shi, L. 968

Shi, X. 16

Shimizu, C, 436

Shin, Ho-Jin 891

Shin, Sang W. 840

Shitara, K. 1074

Shore, N. 327, 328, 326

Shortt, J. 956

Shrestha, Y. 908, 911, 218

Siaplaouras, J. 673

Sibbertsen, F. 120

Sibille, A. 256

Sichward, Lara H. 507

Sicking, A. 380

Siebel, P. 293

Siebenbach, Hans U. 211

Siebert, S. 727, 735

Siebert, U. 947, 955, 1032, 1016

Siebolts, U. 853

Siefer, O. 446

Siegel, D. 534, 560, 208, 709

Siegert, A. 681

Siegle, A. 888

Sieglinde, P. 873

Siegmund, B. 855

Siegrist, M. 548

Siener, R. 852

Siepermann, M. 974, 575

Sieverding, M. 197

Sikic, D. 79

Silber, Y. 669

Silberg, M. 253

Silling, S. 446

Simanovich, E. 329

Šimkovič, M. 374, 414

Simon, R. 1053

Simons, E. 739

Simpson, D. 956

Simson, Barbara W. 92

Singal, Amit G. 32

Singer, S. 656, 658, 804

Sinn, M. 731, 735

Sinner, F. 425, 443

Sivaloganathan, S. 815

Siveke, J. 20, 344, 752, 792

Skarbnik, Alan P. 166

Škaro, A. 579

Skatkova, O. 906

Skikne, B. 287

Skof, Anna S. 764

Sladek, B. 1037

Slamon, D. 309

Sleeman, J. 388

Slomovitz, Brian M. 674

Smeets, R. 312

Smit, D. 120

Smit, H.J.M. 256

Smith, A. 308

Smith, J. 605

Smith, M. 328, 327, 326, 952

Snapir, A. 326

Soerensen, L. 760

Sohoni, S. 411

Sokol, Ethan S. 223

Solar, S. 1062

Solbach, C. 269, 504, 1027

Soldatenkova, V. 255, 277

Solomayer, Erich-F. 426

Solomon, B. 255

Solomon, S. 968, 967

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 281

Sommer, S. 669

Sommerlatte, S. 523, 816, 1039

Song, Yu Q. 891

Sookthai, D. 82, 85, 357

Soysal, Savas D. 104, 89

Spahic, E. 715

Spall, Thomas. 385

Spanier, G. 739

Späth-Schwalbe, E. 171

Speel, Ernst-J. 446

Speer, S. 261

Speiser, D. 397, 572, 722, 1061

Sperk, E. 970, 522, 946

Spiekermann, K. 1041

Spielmann, M. 1022

Spier, I. 379

Spitzner, M. 1

Spix, C. 934

Spohn, Simon K.B. 591

Sprecher, B. 899

Spring, L. 135

Springer, F. 5, 616, 1030

Srinivasan, S. 328

Sroczynski, G. 947, 955, 1032, 1016

Stadelmann-Nessler, C. 815

Stadtmauer, Edward A. 534

Staehler, M. 67, 222

Staemmler, H. 957

Stahl, M. 1074

Stahler, A. 260

Stähler, M. 128

Stahlhut, K. 167

Staib, F. 368

Staib, P. 152, 870

Stalf, H. 673

Stamm, N. 748

Stamm, P. 980

Stammann, C. 204

Stancato, Louis F. 201

Stange, D. 510

Stangenberg, M. 895

Stangl, Gabriele I. 499

Stangner, K. 381

Starbatty, B. 90

Statsenko, G. 908

Stäuber, A. 55

Stauch, M. 869

Stauch, T. 869

Stecher, M. 1014

Steckelberg, A. 499

Stecklum, M. 243

Steeb, T. 456

Steeghs, N. 1064

Steenbuck, Ines D. 586

Stefanjuk, S. 588

Steen, B. 486

Steens, J. 556

Stegen, G. 426

Steger, F. 111, 146

Stegger, L. 943

Stegmann, S. 198

Stehr, Antonia M. 864

Steidl, E. 567

Steifensand, F. 353

Stein, A. 357, 731, 1064, 486, 826

Stein, B. 720, 951

Stein, H. 40

Stein, T. 368

Stein, U. 524, 388, 605

Steinbach, Joachim P. 567

Steinborn, J. 416, 622

Steindorf, K. 197, 1040

Steinecke, M. 156

Steiner, T. 152

Steinestel, K. 959

Steinhagen-Thiessen, E. 159

Steinkasserer, L. 102

Steinmann, D. 547

Stelljes, M. 268

Stemmler, Marc P 864

Stenzinger, A. 413, 482, 707

Stenzl, A. 128, 881

Stepan, L. 967

Stephan, Lars U. 1049, 1052

Stephan-Falkenau, S. 518

Stephanou, M. 157

Sternberg, Cora N. 952

Steurer, S. 1031

Stewart, R. 911

Stickeler, E. 246, 269, 931

Stie, M. 1067

Stief, Christian-G. 359

Stiens, Ray Maria V. 507

Stilgenbauer, S. 349, 411

Stingl, J. 198

Stintzing, S. 103, 260, 563, 624,

1026, 1049, 1052

Stobart, H. 946

Stöckle, M. 128, 195, 556

Stoecklein, Nikolas H. 745

Stoetzer, Oliver J. 306

Stoian, R. 513

Stojadinovic, A. 337

Stoklossa, C. 159

Stöltzing, O. 963

Stolz, R. 547, 720, 951, 692

Stölzel, F. 874

Stössel, S. 673

Stöter, O. 823

Stöver, I. 606, 433

Strack, M. 140, 460, 646

Strahl, A. 895

Strassburg, Christian P. 995, 921

Straßen, U. 272

Stratenwerth, B. 43, 53

Sträter, J. 1066

Straub, M. 735

Strauch, K. 996

Strauß, A. 153, 266

Strebhardt, K. 565, 580

Streckmann, F. 974, 136

Strehl, H. 42

Streitbürger, A. 450, 673

Strewinsky, N. 972

Ströbel, P. 292

Strohbücker, B. 90

Stromberger, C. 262

Stroosma, O. 119

Stroszczynski, C. 813

Strotmann, J. 814

Strueder, Daniel F. 228

Stuhlert, C. 426

Stummer, W. 943

Sturla, S. 53

Sturm, N. 425

Sturmheit, T. 933

Stürzl, M. 864

Stürzl, R. 355

Stuschke, M. 135

Stutz, R. 426

Stüwe, C. 47, 244

Suárez Rodríguez, C. 158, 222

Subbiah, V. 255, 277

Südho, T. 873

Sugg, J. 881

Sültmann, H. 482

Surmann, B. 961, 1056

Surovtsova, I. 177, 390, 392

Surrow, A. 1001

Süß, C. 111, 146

Sütterlin, M. 522

Suzuki, H. 952

Suzuki, K. 971

Swart, E. 934

Symank, J. 512

Symonds, R Paul 946

Szarvas, T. 507

Szymczak, S. 255

Tabatabai, G. 254, 758

Tabernero, J. 1044, 1074

Tahmasbi Rad, M. 580

Tak, Paul P. 758

Takezako, N. 971

Talalaev, N. 705

Talaulicar, R. 1073

Talbot, Christopher J 946, 970

Tam, Constantine S. 374, 349

Tamaskovics, B. 262, 476, 63

Tamborero, D. 916

Tammela, Teuvo L.J. 326, 952

Tammer, I. 809

Tan, P. 956

Tan, X. 516

Tang, D. 281, 282

Tannapfel, A. 523, 788, 1039

Tannert, A. 323

Tat Ling, M. 956

Tatsch, L. 768

Taube, C. 518

Taubert, H. 233

Tauscher, M. 621

Tavenrath, S. 844

Teichert-von Lüttichau, I. 356

Telzerow, E. 359

Templin, M. 325

Tenschert, E. 576

Terhaag, J. 66

Terheyden, P. 544

Terjung, I. 912

Tesch, F. 799

Teschendorf, C. 523

Teschner, A. 86

Teschner, D. 1041

Testa, L. 436

Teufel, A. 10

Tewes, M. 20, 562

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index282

Teynor, A. 180

Thelen, M. 428, 502, 649

Theodoraki, Marie-N. 131

Theoklitou, D. 570

Thiele, S. 952

Thielert, M. 929

Thiemann, E. 269

Thieme, R. 399, 685, 689,

697, 643

Thill, M. 246, 269

Thimme, R. 211, 714

Thol, F. 287

Thomaidou, D. 151

Thomas, J. 131

Thomas, M. 16, 47, 135, 244,

280, 370, 413, 482,

707, 840, 888, 1062

Thomas, S. 275

Thompson, J. 73

Thomsen, Andreas R. 646

Thomssen, C. 751

Thong, M. 532, 358

Thronicke, A. 299, 497, 964

Thul, I. 426

Thuss-Patience, P. 976

Thy, S. 149

Tiede, A. 1022, 975

Tiemann, M. 554

Tietl, J. 200

Tilki, D. 972

Tiller, U.e 568

Tilly, H. 891

Timmermann, B. 450

Timotheou, A. 921

Timrott, K. 601

Ting, S. 344, 507, 752

Tinker, A. 730, 1055

Tirier, S. 737

Todenhöfer, T. 328, 952

Tolaney, S. 936

Toma, M. 921

Tomanek, A. 647

Tomasini, P. 255

Tombal, B. 952

Tometten, L. 1014

Tometten, M. 739

Tomicic, M. 768

Tonk, Christian H. 870, 877, 899

Tonn, Jörg-C. 847, 613

Tonndorf-Martini, E. 47, 244

Topaly, J. 239

Topf, C. 626

Topp, M. 339

Tortora, G. 950

Tothill, Richard W. 223

Touchefeu, Y. 714

Towhidi, T. 1042

Tozzi, A. 640

Traubeck, S. 728

Traxdorf, M. 261

Trebicka, J. 761

Treeck, O. 347

Treese, C. 855

Treiber, H. 465

Tremmel, A. 1065

Trepel, M. 669

Treppner, S. 540

Trillsch, F. 118, 132, 537, 571

Tripal, P. 864

Trněný, M. 891

Trocchi, P. 934

Trojan, J. 443

Trostdorf, K. 171

Trunova, N. 868

Truppel-Hartmann, A. 560, 709, 208

Tschmelitsch, J. 867

Tsiouris, A. 197, 1057

Tsuboi, M. 50

Tubío-Santamaría, N. 323

Tüchler, A. 44

Tufman, A. 728, 989, 1047

Tully, K. 79

Tunn, P.-U. 410

Turnbull, C. 906, 916

Turner, N. 283

Tuschy, B. 522

Tusquets, I. 674

Ubels, J. 415

Uacker, L. 900

Ugidos, M. 287

Ugocsai, P. 903

Ugurel, S. 267

Uhl, N. 1059

Uhl, W. 523, 814, 788

Uhlenbruch, Y. 450

Uhlig, J. 211

Ulbricht, H. 874

Ulbricht, S. 228

Uleer, C. 751

Uller, W. 813

Ullrich, A. 634

Ullrich, R. 690, 700

Ulys, A. 326

Ungar, N. 197

Ungelenk, M. 323

Unger, C. 229

Unger, S. 307

Unsöld, L. 888

Untch, M. 504, 1027

Urban, L. 920

Urbschat, I. 354

Ursol, G. 16, 33

Usenko, G. 414

Utikal, J. 73, 267

Uttinger, K. 396

Uxa, S. 381

Valdagni, R. 946

Valenta, S. 180

Valentini, J. 720, 951

Vallieres, E. 33

van Boemmel, F. 425

Van Cutsem, E. 950, 1044

van de Donk, Niels W.C.J. 534

Van den Bosch, V. 119

Van den Eertwegh, A. 151

van Oorschot, B. 1062

van Troostenburg, A. 252

Vasiliev, A. 16

VAsiljeva, K. 346, 294, 351

Vattai, A. 828

Vcev, A. 579, 760

Vecchione, L. 260, 563, 1026

Vega, A. 970, 946

Vehreschild, Jörg J. 1014, 1041

Vehreschild, M. 1041

Velarde, Luis Enrique C. 868

Velcheti, V. 989

Veldeman, L. 970, 946

Veltrup, E. 94

Veltzke-Schlieker, W. 855

Veneris, J. 730, 990, 1055

Venerito, M. 59, 425, 443

Venkataramani, V. 1008

Verholen, F. 327

Verret, W. 32

Verzoni, E. 151

Veselinovic, K. 1059

Vetter, M. 751

Viale, G. 210

Viestenz, A. 853

Viezens, L. 895

Villalobos-Bollen, M. 888

Virchow, I. 276, 344, 507, 752, 867

Vjaters, E. 326, 328, 327

Vogel, A. 103, 990

Vogel, P. 150, 691

Vogel, T. 390

Vogelhuber, M. 339

Vogl, I. 902

Vogt, T. 648

Voigt, M. 934

Voigtländer, S. 618

Voiss, P. 547, 692

Voit, F. 1014

Voitko, O. 908

Voland, A. 614, 617, 741

Volk, A. 663

Völkl, S. 31

Volkmer, Anne K. 785

Vollkommer, T. 312

Vollmann-Zwerenz, A. 613

Voltz, R. 634

vom Endt, C. 884

von Amsberg, G. 972

von Baumgarten, L. 537, 555

von Bergwelt-Baildon, M. 428, 502, 537,

649, 1041

von Brandenstein, M. 661, 698, 701,

708, 711, 715

von Bubno, N. 603, 1042

von der Assen, A. 522

von der Brelie, C. 465

von der Grün, J. 476, 63

von der Heyde, E. 67, 63, 266, 869, 103

von Havranek, M. 134

von Krosigk, V. 385

von Levetzow, C. 912

von Lilienfeld-Toal, M. 1014, 1041

von Meyenn, M. 906, 916

von Moos, R. 73

von Suchdoletz, H. 1007

von Trott, P. 497

von Witzleben, A. 131

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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 283

Vordermark, D. 474, 499

Vorwergk, J. 662

Vosbeck, J. 89

Voß-Böhme, A. 639

Vucinic, V. 5

Vucinic, V. 610

Vulsteke, C. 674

Vynnychenko, I. 33

Vynnytska-Myronovska, B. 195

Wabinga, H. 823

Wach, M. 414

Wach, S. 233

Wachter, A. 815

Wacker, F. 852

Waddell, T. 158

Wagenpfeil, G. 426

Wagner, Anna D. 103

Wagner, Anne-C. 648

Wagner, D. 411

Wagner, D. 812

Wagner, J. 712

Wagner, Johannes M. 251

Wagner, Sa. 535

Wagner, S. 715

Wagner, S. 446

Wahib, R. 933

Wahlen, S. 914

Waidmann, O. 425, 443

Wainberg, Z. 1044

Wakelee, H. 33

Walawgo, T. 519

Waldenberger, D. 265

Waldenberger, D. 63

Walding, A. 50

Waldmann, A. 532

Walker, G. 210

Walker, P. 166

Waller, C. 1007

Wallis, M. 419

Wallwiener, D. 676

Wallwiener, M. 851

Walter, J. 568

Walter, J. 275

Walter, Robert Fred H. 416

Walter, S. 453

Walther, W. 201, 404, 524, 605

Walz, T. 659

Wang, G. 864

Wang, J. 151

Wang, J. 560, 208

Wang, Michael L. 516

Wang, Min H. 166, 414

Wang, P. 636

Wappenschmidt, B. 361

Ward, T. 970, 946

Warfsmann, J. 380

Warwas, Karsten M. 86

Waszak, A. 989

Watolla, M. 380

Webb, A. 970, 946

Weber, C. 456

Weber, F. 347

Weber, F. 604

Weber, Jan-P. 912

Weber, K. 761

Weber, M. 458, 493, 739

Weber, V. 862

Weberpals, J. 916

Wedding, U. 1039

Wedeken, L. 325, 524, 678, 718

Weder, W. 50

Wedig, T. 829

Wegener, N. 1023

Weger, K. 604

Weg-Remers, S. 415

Wegwitz, F. 588

Wehler, T. 370

Wei, Andrew H. 956, 287

Wei, R. 436

Weichenthal, M. 267

Weichert, W. 280, 114

Weide, R. 936

Weigel, M. 269

Weigert, E. 751

Weigmann-Faßbender, S. 874

Weiler, D. 277

Weiler, M. 1040

Weiler, N. 456

Weinke, M. 79

Weinkove, R. 374

Weirda, William G. 349

Weis, I. 851

Weisel, K. 150, 691, 709

Weiskirchen, R. 931

Weiss, C. 10, 522

Weiß, D. 586

Weißbach, J. 403

Weißbach, L. 204

Weitz, J. 787

Welker, L. 895

Wellesen, A. 134

Wellner, U. 1009

Welslau, M. 867, 869, 103, 63,

239, 612, 898, 414

Welt, A. 246

Wendler, O. 432

Wendling, J. 752

Wennhold, K. 428

Wensing, M. 204

Wenz, F. 522

Wenzel, C. 510

Wenzel, Gentiana I. 648

Werbrouck, P. 327

Werle, L. 1069, 1075, 866

Wermke, M. 370, 510, 690, 700

Werner, J. 219

Werner, T. 586

Werry, Jan-E. 458

Wesseler, C. 280

Wessels, S. 413

Wessolly, M. 199, 416, 518, 622

West, Catharine ML 946, 970

Westbrook, K. 309

Westphalen, B. 223, 537, 555, 779

Weth, J. 485

Wetzel, N. 67, 245, 259

Wetzig, S. 157

Weydandt, L. 190

Weykamp, F. 578

Whipple Neibauer, M. 337

White, D. 150

Whitston, D. 911

Wichmann, D. 593

Wichmann, G. 262

Wichmann, Y. 689

Wick, W. 1008

Wiedenmann, B. 855

Wiedenmann, N. 513

Wieditz, J. 1062

Wiegand, J. 266

Wiegand, S. 262

Wiegering, A. 396

Wiek, C. 561

Wieland, T. 902

Wieland, U. 446

Wienands, J. 1

Wienands, L. 180

Wiener, A. 673

Wiesweg, M. 276, 344, 518, 752

Wild, M. 828

Wild, Philipp S. 997

Wilde, F. 959

Wilhelm, M. 721, 506

Wilhelm, M. 40

Wilhelm, M. 177

Wilke, J. 280

Will, R. 749

Willborn, K. 694, 712

Wille, K. 1014

Willich, Stefan N. 159

Willimsky, G. 681

Willy, C. 869

Wilms, G. 204

Wiltink, J. 996, 1057

Wimberger, P. 291, 302, 676

Winde, G. 170

Winder, T. 103

Windisch, P. 360

Winer, E. 309

Winkler, Eva C. 961, 1056, 415

Winkler, F. 1008

Winkler, M. 547, 692

Winnand, P. 739

Winquist, E. 308

Winter, H. 482

Winter, M. 1064

Winzler, Cl. 392

Wirsik, N. 1002

Wirth, L. 277

Wirth, M. 152

Wirtz, R. 79, 94

Wirtz, S. 761

Wiskemann, J. 614, 617, 630, 673,

741, 1040, 321, 197

Wisser, S. 523

Wißmann, N. 1008

Witkowski, L. 788

Witt, C. 547

Witt, O. 749, 628

Witte, D. 788

Wittekindt, C. 446

Witteler, R. 302

Wittke, K. 159

Wittke, T. 673

Witzel, I. 312

Wlochowitz, D. 815

Wöckel, A. 246, 656, 658

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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index284

Wodlej, C. 404

Wohlschlaeger, J. 416, 518, 622

Woldai, S. 889

Wolf, C. 100

Wolf, J. 255, 510, 912

Wolf, T. 259

Wolfarth, B. 159, 791

Wölfel, T. 410

Wolfer, S. 566

Wol, A.r 815

Wol, M. 874

Wol, T. 239, 867

Wömpner, C. 912

Wong, A. 553

Wong, S. 308

Woopen, H. 159

Wördeho, H. 74

Wörmann, B. 1039

Wörmann, C. 426

Wortmann, A. 82

Wöstemeier, A. 1035

Woyach, Jennifer A. 349, 166, 516

Wright, Gail. S. 636

Wright, J. 277

Wrobel, D. 66

Wu, K. 374

Wu, Yi-L. 840

Wuerein, D. 94

Wulf-Goldenberg, A. 243

Wullich, B. 79, 233

Wunderlich, H. 556

Würdemann, N. 446

Wurm-Kuczera, R. 467

Würstlein, R. 49, 298, 537,

555, 877

Wüstefeld, H. 964

Xie, M. 908, 911

Xu, Q. 12

Y. Locker, G. 950

Yachnin, J. 690, 700

Yakoub-Agha, I. 709

Yang, Cheng-Ta 16

yang, c. 685

Yang, James Chih-H. 840

Yang, L. 380, 590, 740, 745

Yao, D. 971

Yao, R. 260, 563

Yatabe, Y. 50

Ye, D. 952

Yecies, J. 374

Yesilyurt, Umut U. 1001

Yew Fong, C. 956

Yildirim, A. 328

Yılmaz-Aslan, Y. 835, 1068

Ying Tan, S. 956

Yordanova, K. 648

Yu, H. 219

Yu, T. 166, 414

Yu, T. 608

Yushak, Melinda L 690, 700

Zaccagnino, A. 195

Zacharias, S. 280

Zahn, Mark-O. 246, 82, 135

Zaiss, M. 246, 66

Zaman, K. 66

Zamboglou, C.os 591

Zander, T. 810

Zaoui, K. 360

Zapfe, L. 986

Zaun, G. 276, 344, 752

Zdioruk, M. 758

Zeidler, R. 943

Zeindler, J. 89

Zeiser, R. 307

Zeissig, Sylke R. 532, 1009

Zeitler, G. 94, 777

Zemlin, C. 426

Zemlin, M. 426

Zemojtel, T. 260

Zemskov, S. 1009

Zeng, L. 50

Zengerling, F. 79

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